N,N-dialkyl-N′-chlorosulfonylchloroformamidines in heterocyclic synthesis. II. Thiazolo-, thiadiazolo-, and oxadiazolo-fused [1,2,4,6]thiatriazine dioxides

Article abstract of DOI:10.1071/CH05070

N,N-dialkyl-N′-chlorosulfonylchloroformamidines 1 were treated with 2-aminothiazoline, 2-aminothiazoles, 2-aminobenzothiazoles, 2-amino-1,3,4- thiadiazoles, and 2-amino-1,3,4-oxadiazoles to give a 6,7-dihydrothiazolo[3,2-b] [1,2,4,6]thiatriazine dioxide 3

Full text of DOI:10.1071/CH05070

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2005, 58, 891–900
N,N-Dialkyl-Nꢀ-Chlorosulfonylchloroformamidines in
Heterocyclic Synthesis. II. Thiazolo-, Thiadiazolo-, and
Oxadiazolo-Fused [1,2,4,6]Thiatriazine Dioxides
Gary D. Fallon,A Craig L. Francis,B,C Katarina Johansson,B Andris J. Liepa,B,C
and Ruth C. J. WoodgateB
A School of Chemistry, Monash University, Clayton VIC 3800, Australia.
B CSIRO Molecular and Health Technologies, Clayton South VIC 3168, Australia.
C Corresponding authors. Email: craig.francis@csiro.au; andy.liepa@csiro.au
N,N-dialkyl-Nꢀ-chlorosulfonylchloroformamidines 1 were treated with 2-aminothiazoline, 2-aminothiazoles,
2-aminobenzothiazoles, 2-amino-1,3,4-thiadiazoles, and 2-amino-1,3,4-oxadiazoles to give a 6,7-dihydrothiazolo-
[3,2-b][1,2,4,6]thiatriazine dioxide 3, a 6,7-dihydrothiazolo[2,3-c][1,2,4,6]thiatriazine dioxide 4, thiazolo[3,2-b]-
[1,2,4,6]thiatriazine dioxides 5, [1,2,4,6]thiatriazino[3,2-b]benzothiazole dioxides 7, a [1,2,4,6]thiatriazino-
[3,4-b]benzothiazole dioxide 8, [1,3,4]thiadiazolo[2,3-c][1,2,4,6]thiatriazine dioxides 10, [1,3,4]thiadiazolo[3,2-b]-
[1,2,4,6]thiatriazine dioxides 11, [1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine dioxides 13, and [1,3,4]thiadiazolo-
[3,2-b][1,2,4,6]thiatriazine dioxides 14. Compounds 3, 4, 5, 7, 8, 10, 11, 13, and 14 are derivatives of new ring
systems.
Manuscript received: 4 March 2005.
Final version: 23 May 2005.
R2N
Introduction
R2N
Cl
Me2N
Et2N
1a
1b
SO2Cl2
R2N
N
The key role played by heterocyclic compounds in the quest
for applications in biological activity, optics, electronics, and
material sciences is well recognized.[1–4] Accordingly, con-
siderable research effort continues to be directed towards the
discovery of new synthetic routes to novel heterocyclic com-
pounds. As part of our ongoing interest in the synthesis of
such molecules, we have been evaluating N,N-dialkylated
Nꢀ-chlorosulfonylchloroformamidines1, whichembodyread-
ily available[5,6] but rarely used[7–9] 1,3-dielectrophiles. In
Part I[10] of this series we described reactions between 1
and two types of 1,2-dinucleophile as a route to uncom-
mon five-membered heterocycles. Hence treatment of 1 with
either hydrazines or hydroxamic acids was found to give
[1,2,3,5]thiatriazole dioxides and [1,3,2,4]oxathiadiazole
dioxides, respectively.[10]
NSO2Cl
N
1c
1
1d
N
Scheme 1.
Treatment of 1b with 2-amino-2-thiazoline 2a in
dichloromethane in the presence of triethylamine provided
the hitherto unknown ring systems 6,7-dihydrothiazolo-
[3,2-b][1,2,4,6]thiatriazine dioxide 3 and the isomeric 6,7-
dihydrothiazolo[2,3-c][1,2,4,6]thiatriazine dioxide 4 in 18
and 8% yields, respectively (Scheme 2).
Treatment of the dichlorides 1 with 2-aminothiazole deriv-
atives 2b, 2c under the same conditions afforded thiazolo-
[3,2-b][1,2,4,6]thiatriazine dioxides 5 (Scheme 3, Table 1).
However, the possible isomeric minor products, thiazolo-
[2,3-c][1,2,4,6]thiatriazine dioxides 6, were not observed.
A similar reaction of the dichlorides 1 with 2-
aminobenzothiazole derivatives 2d–2f using either the above
conditions or N,N-diisopropylethylamine in 1,3-dimethyl-
3,4,5,6-tetrahydro-2(1H)-pyrimidinone (dimethylpropylene
urea, DMPU), gave[1,2,4,6]thiatriazino[3,2-b]benzothiazole
dioxides 7 as major products and also the isomeric
[1,2,4,6]thiatriazino[3,4-b]benzothiazole dioxides 8 as a
minor product in at least one instance (Scheme 4, Table 2).
Each of 5, 7, and 8 represent novel heterocycles.
It was apparent that an analogous cyclization might be
effected between 1 and suitable 1,3-dinucleophiles to furnish
a route to six-membered heterocycles.
We now report upon some reactions of 1 with several 2-
amino-1-azaheterocycles, which are well known to manifest
the characteristics of a 1,3-dinucleophilic system.
Results and Discussion
The dichlorides (1a–1d) were readily prepared[5,6,10] from
sulfuryl chloride and the corresponding dialkyl cyanamide
(Scheme 1).
© CSIRO 2005
10.1071/CH05070
0004-9425/05/120891

892
G. D. Fallon et al.
S
N
Cl
NH2·HBr
N
N
S
N
N
S
Et3N
S
S
ϩ
ϩ
DCM
N
N
N
N
NSO2Cl
N
O
O
O
O
1b
2a
3
4
Scheme 2.
R3
R4
R2
R2
R2
N
S
N
H2N
N
N
N
S
S
R1
R1
Cl
Et3N
R3
R3
R1
N
N
N
N
N
ϩ
DCM
S
S
NSO2Cl
R4
R4
O
O
O
O
1
2b, 2c
5
6
Scheme 3.
R3
NH2
R2
N
R2
R2
N
Et3N
DCM
S
N
N
N
S
S
N
S
Cl
NSO2Cl
R1
R1
R1
ϩ
ϩ
or
N
N
N
N
Pr2iNEt
DMPU
S
R3
O
O
O
O
R3
1
2d–2f
7
8
Scheme 4.
Table 1. Synthesis of the thiazolo[3,2-b][1,2,4,6]thiatriazine
Table 2. Synthesis of the [1,2,4,6]thiatriazino[3,2-b]benzothiazole
dioxides 5
dioxides 7
R1R2N
R3
R4
Product(s) Yield(s) [%]
R1R2N
R3
Product(s)
Yield(s) [%]
12
Me2N (1a)
Et2N (1b)
H
Me
CH2CO2Et (2b)
Me (2c)
5a
5b
15
14
Cl (2d)
7a
N
(1c)
(1c)
Me
Me
Me (2c)
Me (2c)
5c
41
44
N
(1c)
OEt (2e)
H (2f)
7b (+ 8b)
33 (+ 4)
N
N
5d
N
7c
38
(1d)
(1d)
The representatives of the heterocyclic systems 3, 4, 5,
7, and 8 were all stable, colourless, crystalline solids which
showed no signs of decomposition after being stored for
many months at room temperature and were also unaffected
by recrystallization from boiling alcohols. In general, the
compounds were soluble in chloroform and dichloromethane
but rather less so in either diethyl ether or ethyl acetate.
The dichlorides 1 have two reactive sites and cyclization
may result in two isomeric ring systems. Nuclear magnetic
resonance spectroscopic studies failed to provide convincing
assignments and consequently unequivocal determination
of structures was based on X-ray crystallographic analyses
of representative compounds (Fig. 1, Table 5). The results
indicated that the major cyclization product formed from a
reaction of the amino group of 2 with the amidinyl chloride
moiety of 1 and reaction of the ring nitrogen with the sulfonyl
chloride.
The exocyclic nitrogen atom of 2-aminothiazoles is known
to be the preferred site of reaction with reagents bear-
ing an sp2 C electrophilic centre (e.g., acid chlorides,
formimidates).[11,12] Steric factors are also known to influ-
ence selectivity during reactions of 2-aminothiazoles with
ambident electrophilic reagents.[11] The formation of com-
pounds 5 and 7 is consistent with these observations and the

N,N-Dialkyl-Nꢀ-Chlorosulfonylchloroformamidines in Heterocyclic Synthesis
893
R3
S
R2
R2
N
R2
N
N
Na2CO3
DMF, rt
N
N
S
Cl
H2N
N
S
N
S
N
R1
R1
R1
ϩ
R3
ϩ
R3
or
DMPU
⌬
NSO2Cl
N
N
N
N
N
S
O
O
O
O
1
9
10
11
Scheme 5.
Table 3. Synthesis of the [1,3,4]thiadiazolo[2,3-c][1,2,4,6]thia-
group with the sulfonyl chloride moiety. Curiously, this is the
opposite regiochemistry from that observed in the thiazole
series.
triazine dioxides 10
R1R2N
R3
Product(s)
Yield(s) [%]
Me2N (1a)
Me2N (1a)
Me2N (1a)
Et2N (1b)
Et (9a)
10a
10b
13
31
The relative reactivity of the two electrophilic chlorine-
bearing sites in formamidines 1 is not clearly defined. Some
literature precedent suggests, on the basis of infrared spec-
troscopic analysis, a greater susceptibility of the sulfonyl
chloridemoietyin 1towardsnucleophilicattackbysecondary
amines such as morpholine and piperidine.[7] On the other
hand, a preferred reactivity of the chloroamidine moiety of
1 towards secondary amines has been proposed[9] from an
analysis of mass spectrometric fragmentation. In Part I[10]
of this series the synthesis of [1,2,3,5]thiatriazole dioxides
was described as resulting from regioselective reaction of
1 with monosubstituted acyl and aryl hydrazines. In those
reactions, cyclization proceeded such that the unsubstituted
nitrogen atom of the hydrazine bonded to the amidine car-
bon atom of 1 while the substituted site reacted with the
sulfonyl chloride. In general, monosubstituted acyl and aryl
hydrazines react with electrophiles at the unsubstituted amino
group.[13,14] These findings, together with those quoted in
the above reference[9] indicate that the chloro-substituted
amidine carbon atom of 1 is the electrophilic site more reac-
tive towards nitrogenous nucleophiles. The N-3 atom of the
2-amino[1,3,4]thiadiazoles is known to have greater nucle-
ophilicity than the exocyclic nitrogen atom,[15] so our results
seem consistent with these findings. In addition, since N-4
has no substituent in the starting materials 9, there is little
steric impediment to the formation of products 10.
But (9b)
SEt (9c)
Me (9d)
10c (+ 11c)
42 (+ 10)
10d (+ 11d)
23 (+ 4)
Et (9a)
10e
10f
29
29
N
(1d)
SEt (9c)
N
(1d)
much lower yields of 8 may be at least partly due to steric hin-
derance between the substituent at C-4 of the thiazole ring and
the dialkylamino moiety. The significant proportion of com-
pound 4 formed in the reaction of 1b with 2a (Scheme 2) adds
some support to this argument, since C-4 of aminothiazoline
2a is unsubstituted.
A related reaction between dichlorides 1 and 2-amino-
[1,3,4]thiadiazoles 9 in either N,N-dimethylformamide
(DMF)/sodium carbonate or DMPU (without added
base) provided [1,3,4]thiadiazolo[2,3-c][1,2,4,6]thiatriazine
dioxides 10 as the major product with the isomeric
[1,3,4]thiadiazolo[3,2-b][1,2,4,6]thiatriazine dioxides 11
found as minor products in at least two cases (Scheme 5,
Table 3).
The examples of the novel ring systems 10 and 11
described above were again colourless, crystalline solids hav-
ing similar stability and solubility properties to the thiazolo-
fused systems described earlier. The major products 10 were
less soluble than the minor products 11 and this allowed
selective precipitation of the major products directly from
the reaction mixture. In two cases the minor product 11 was
isolated from the mother liquors by evaporation followed by
chromatographic purification of the residue.
Having successfully synthesized fused thiatriazines from
dichlorides 1 and 2-amino[1,3,4]thiadiazoles 9, we turned
our attention to the analogous reaction of 1 with 2-amino-
[1,3,4]oxadiazoles 12. This reaction in DMPU led to [1,3,4]-
oxadiazolo[2,3-c][1,2,4,6]thiatriazine dioxides 13 as the
major product and the isomeric [1,3,4]oxadiazolo[3,2-b]-
[1,2,4,6]thiatriazine dioxides 14 as the minor product in at
least one case (Scheme 6, Table 4).
The examples of the novel ring systems 13 and 14
described above were all colourless, crystalline solids
having similar stability and solubility properties to the
analogous thiazolo- and thiadiazolo-fused systems. As with
the thiadiazole chemistry described earlier, the major prod-
ucts 13 were less soluble than the minor products 14 and this
usually allowed selective precipitation of the major products
directly from the reaction mixture. In one instance, the minor
product 14 was obtained from the mother liquor by evapora-
tion followed by chromatographic purification of the residue.
Again, assignment of structures was based on X-ray
crystallographic analyses of representative compounds
(Fig. 2, Table 5), solubility properties, and behaviour
during thin-layer chromatography (TLC). In general, the
[1,3,4]thiadiazolo[2,3-c][1,2,4,6]thiatriazines 10 were rather
less mobile during TLC than the isomeric [1,3,4]thiadiazolo-
[3,2-b][1,2,4,6]thiatriazines 11.
These results revealed that the major reaction pathway
involved reaction of a ring nitrogen of 9 with the amidine
carbon atom of 1 and concomitant reaction of the amino

894
G. D. Fallon et al.
R3
O
R2
N
R2
N
R2
N
N
N
N
S
Cl
H2N
O
N
O
DMPU
R1
R1
R1
ϩ
ϩ
R3
R3
⌬
NSO2Cl
N
N
N
N
N
N
S
O
O
O
O
1
12
13
14
Scheme 6.
Table 4. Synthesis of the [1,3,4]oxadiazolo[2,3-c][1,2,4,6]thia-
these domains and some other related cyclizations will form
the basis of subsequent reports.
triazine dioxides 13
R1R2N
R3
Product(s)
Yield(s) [%]
Experimental
Me2N (1a)
Me2N (1a)
Me2N (1a)
Bn (12a)
13a
13b
13c
80
23
27
4-But-Ph (12b)
(E)-1-methyl-2-
phenylvinyl (12c)
Bn (12a)
Methods and Materials
Melting points were determined on a Gallenkamp MPD350.BM2.5
apparatus and are uncorrected. Analytical thin layer chromatography
(TLC) was carried out on Macherey–Nagel Polygram pre-coated plas-
tic sheets (0.2 mm layer of silica gel with fluorescent indicator UV254).
Developed plates were visualized with either UV light (254 nm) or a
solution of 10% (w/v) phosphomolybdic acid in ethanol followed by
heating. Radial chromatography was performed on a Harrison Research
Chromatotron (Model 7924T) using 1, 2, or 4 mm thick silica plates
(Merck silica gel 60 PF254 containing gypsum). 1H NMR spectra were
recorded at room temperature on a Bruker AC-200 spectrometer oper-
ating at 200 MHz using CDCl3 as solvent and internal reference unless
otherwise specified. 13C NMR spectra were recorded at room temper-
ature on a Bruker Av400 spectrometer operating at 100.6 MHz using
CDCl3 as solvent and internal reference unless otherwise specified.
Some 13C NMR spectra were recorded on a Bruker DRX500 spectro-
meter operating at 125.75 MHz. Positive ion electron impact (EI) mass
spectra were run on aThermoQuest MAT95XL mass spectrometer using
an ionization energy of 70 eV. Only the major fragments are given with
their relative abundances shown in parentheses.Accurate mass measure-
ments were obtained with a resolution of 5000–10 000 using perfluoro-
kerosene as the internal reference. Microanalyses were performed at the
Campbell Microanalytical Laboratory, University of Otago.
Et2N (1b)
Et2N (1b)
13d (+ 14d)
37 (+ 5)
2-thienyl (12d)
13e
48
Ph (12e)
13f
85
72
N
(1d)
4-But-Ph (12b)
13g
N
(1d)
As before, assignment of structures was based on
X-ray crystallographic analyses of representative compounds
(Fig. 3, Table 7), solubility properties, and behaviour during
TLC. The [1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine diox-
ides 13 were generally much less mobile on TLC than the
isomeric [1,3,4]oxadiazolo[3,2-b][1,2,4,6]thiatriazine diox-
ides 14.
These results indicated that the major reaction pathway
involved bonding by the ring nitrogen of 12 to the amidine
carbon atom of 1 while the amino group reacted with the
sulfonyl chloride moiety, which is consistent with the major
pathway in the analogous thiadiazole chemistry described
earlier.
Crystal data were collected on a Nonius Kappa CCD fitted with
graphite monochromatized MoKα radiation, λ 0.71073 Å. The structure
was solved by direct methods and refined by a full-matrix, least-squares
procedure based on F2.[16,17] All non-hydrogen atoms were assigned
anisotropic temperature factors in each case and hydrogen atoms
were included in calculated positions. Crystallographic data (excluding
structural factors) for all structures have been deposited with the Cam-
bridge Crystallographic Data Centre. Deposition numbers are listed in
Tables 5–7. Copies may be obtained without charge from CCDC, Union
Road, Cambridge CB2 1EZ, UK (e-mail: deposit@ccdc.cam.ac.uk).
Petroleum spirit refers to a fraction boiling between 40 and 60◦.
All organic extracts were dried over anhydrous magnesium sulfate
unless otherwise stated. N,N-Dialkyl-Nꢀ-(chlorosulfonyl) chlorofor-
mamidines 1a–1d were prepared by literature procedures[5,6,10] and
used as crude products. The deterioration of these compounds and sub-
stantial losses during attempted purification outweighed the benefits
of increased purity. Other materials were obtained from commercial
sources or by procedures described in the literature.
Conclusions
The dichloro compounds 1 have been shown to react as 1,3-
dielectrophiles with a variety of five-membered 2-amino-1-
azaheterocycles resulting in regioselective formation of new,
stable, fused thiatriazines.
Several different sets of reaction conditions were investi-
gated during the preparation of the fused thiatriazine prod-
ucts, and they all afforded the desired products. However,
no systematic study to compare the relative yields or isomer
ratios for different sets of reaction conditions was undertaken
astheprincipalfocusoftheinvestigationwasuponthediscov-
ery and rapid acquisition of novel compounds for biological
screening.
General Synthesis Method A
Triethylamine (11 mmol) was added to a stirred solution of the
2-aminothiazole hydrobromide 2 (3.33 mmol) and the dichloro com-
pound 1 (4.33 mmol) in dichloromethane (5 mL). The resulting mixture
was stirred for 3 days at room temperature, evaporated, and the residue
was partitioned between dichloromethane and water. The organic layer
was dried and evaporated under reduced pressure. The residue was
purified by radial chromatography. Elution with 0–5% ethyl acetate
in dichloromethane afforded the title compounds, which were further
purified by recrystallization.
While the dinucleophiles used in this work were derived
from five-membered heterocycles, it is apparent that this
methodology may be extended to include six-membered
2-amino-1-azaheterocycles. The results from exploration of

N,N-Dialkyl-Nꢀ-Chlorosulfonylchloroformamidines in Heterocyclic Synthesis
895
C6
C5
C10
C9
N4
N2
C7
N2
S2
C4
N4
C1
S2
C4
C2
C2
C1
C8
C7
C3
C8
C6
N3
N1
C3
C5
N3
N1
S1
S1
O2
O1
O1
O2
3
5b
C111
C101
S21
C41
C121
N41
N21
C21
C31
C11
C81
C71
C91
N31
N11
S11
O21
Cl11
C61
C51
O11
7a
Fig. 1. ORTEP diagrams of 3, 5b, and 7a.
Table 5. Crystal data and structure refinement for 3, 5a, 5b, 7a, 7c
Parameter
3
5a
5b
7a
7c
CCDC deposition no.
Empirical formula
Formula weight
Temperature [K]
Wavelength [Å]
Crystal system
Space group
Unit cell dimensions
a [Å]
272512
C8H14N4O2S2
262.35
272510
C10H14N4O4S2
318.37
272508
C10H16N4O2S2
288.39
123(2)
0.71073
Orthorhombic
Pbca
272509
C12H11ClN4O2S2
342.82
123(2)
0.71073
Monoclinic
P21/n
272511
C13H14N4O2S2
322.40
123(2)
123(2)
123(2)
0.71073
Monoclinic
P21/c
0.71073
Triclinic
P1
0.71073
Monoclinic
P21
10.2058(2)
8.2678(2)
14.6944(4)
90
110.172(2)
90
1163.85(5)
4
1.497
7.6746(2)
8.6436(2)
11.4599(3)
105.3151(8)
102.9273(11)
106.5765(13)
664.95(3)
2
1.590
0.420
0.40 × 0.30 × 0.20
3.68 to 28.19
12573
8.2382(1)
22.8763(3)
14.2281(2)
90
90
90
2681.42(6)
8
1.429
11.4227(1)
16.9832(2)
14.0735(2)
90
93.1990(10)
90
2725.92(6)
8
1.671
8.6504(1)
25.6693(4)
9.3426(1)
90
97.7271(6)
90
2055.68(5)
6
1.563
b [Å]
c [Å]
α [◦]
β [◦]
γ [◦]
Volume [Å3]
Z
Density (calc.) [mg m−3
]
Absorption coeff. [mm−1
Crystal size [mm3]
θ range [◦]
]
0.450
0.398
0.596
0.399
0.25 × 0.20 × 0.16
2.87 to 28.20
24309
2840
0.0423
0.38 × 0.33 × 0.22
3.56 to 28.16
29790
3267
0.0440
3267
0.25 × 0.15 × 0.12
2.24 to 28.21
38190
6642
0.0501
0.27 × 0.21 × 0.18
3.80 to 28.17
23276
9849
0.0392
Reflections collected
Independent reflections
R(int)
3221
0.0428
3221
No. of reflections included
2840
6642
9849
in refinement
Final R indices [I > 2σ(I)]
R1
wR2
0.0254
0.0660
0.0372
0.0977
0.0326
0.0795
0.0544
0.1322
0.0368
0.0740
R indices (all data)
R1
wR2
0.0297
0.0687
1.061
0.0441
0.1029
1.032
0.0464
0.0858
1.036
0.0742
0.1409
1.173
0.0497
0.0783
1.052
−0.04(4)
Goodness-of-fit on F2
Absolute structure parameter

896
G. D. Fallon et al.
The following compounds were prepared by the above procedure:
General Synthesis Method B
A mixture of the 2-aminobenzothiazole 2d, 2e (2.3 mmol), the dichloro
compound 1 (2.76 mmol), and N,N-diisopropylethylamine (5.52 mmol)
in DMPU (3 mL) was stirred at room temperature for 2 days. Ethyl
acetate (10 mL) was stirred in, followed by water (10 mL). The resulting
mixture was stirred at room temperature for 1 h and the precipitate was
collected by filtration and washed with ethyl acetate.The solid was puri-
fied by radial chromatography, eluting with dichloromethane to provide
the title compounds, which were further purified by recrystallization.
The following compounds were prepared by the above procedure:
3-Diethylamino-6,7-dihydro-1,1-dioxo-1H-1λ6-thiazolo[3,2-b]-
[1,2,4,6]thiatriazine 3 and 4-diethylamino-6,7-dihydro-2,2-
dioxo-2H-2λ6-thiazolo[2,3-c][1,2,4,6]thiatriazine 4
Compound 3: recrystallized from ethanol, 18% yield, mp 133.5–
134◦C. (Found: C 36.9, H 5.3, N 21.4%, M+• 262.0548. C8H14N4O2S2
requires C 36.6, H 5.4, N 21.4%, M+• 262.0553.) δH 4.37 (2H, t, J 7.5,
CH2), 3.58 (2H, q, J 7, NCH2), 3.52 (2H, q, J 7, NCH2), 3.30 (2H, t,
J 7.5, CH2), 1.21 (3H, t, J 7, CH3), 1.16 (3H, t, J 7, CH3). δC 172.9,
156.5, 49.0, 42.9, 42.6, 24.4, 13.7, 12.6. m/z (EI+) 262 (45%, M+•), 247
(100), 219 (48).
7-Chloro-1,1-dioxo-3-pyrrolidin-1-yl-1H-1λ6-
[1,2,4,6]thiatriazino[3,2-b]benzothiazole 7a
Compound 4: recrystallized from ethyl acetate, 8% yield, mp
•
195.5–196.5◦C. (Found: C 36.8, H 5.3, N 21.3%, M+ 262.0546.
Recrystallized from ethyl acetate, 12% yield, mp gradual decom-
position >260◦C. (Found: C 42.2, H 3.2, N 16.4%. C10H16N4O2S2
requires C 42.0, H 3.2, N 16.3%.) δH ([D6]DMSO) 8.19 (1H, d, J 2,
ArH), 7.80 (1H, d, J 9, ArH), 8.19 (1H, dd, J 9, 2, ArH), 3.69–3.59 (2H,
m, NCH2), 3.54–3.44 (2H, m, NCH2), 1.97–1.87 (4H, m, CH2CH2). δC
168.2, 153.1, 132.8, 130.2, 128.2, 123.5, 122.8, 115.8, 47.6, 47.4, 24.7,
24.4. m/z (EI+) 342/344 (72/30%, M+•), 209/211 (85/31), 70 (100).
•
C8H14N4O2S2 requires C 36.6, H 5.4, N 21.4%, M+ 262.0553.) δH
4.24 (2H, t, J 6.5, CH2), 3.32 (2H, t, J 6.5, CH2), 3.29 (4H, q, J 7,
2 × NCH2), 1.25 (6H, t, J 7, 2 × CH3). δC 167.0, 152.9, 52.4, 44.5, 25.2,
12.7. m/z (EI+) 262 (2%, M+•), 247 (3), 233 (8), 219 (14), 183 (100).
3-Dimethylamino-7-ethoxycarbonylmethyl-1,1-dioxo-1H-1λ6-
thiazolo[3,2-b][1,2,4,6]thiatriazine 5a
1,1-Dioxo-7-ethoxy-3-pyrrolidin-1-yl-1H-1λ6-
[1,2,4,6]thiatriazino[3,2-b]benzothiazole 7b and
2,2-Dioxo-8-ethoxy-4-pyrrolidin-1-yl-2H-2λ6-
[1,2,4,6]thiatriazino[3,4-b]benzothiazole 8b
Recrystallized from ethanol, 15% yield, mp 137.5–138.5◦C. (Found:
C 37.8, H 4.3, N 17.5%, M+• 318.0445. C10H14N4O2S2 requires C 37.7,
•
H 4.4, N 17.6%, M+ 318.0451.) δH 6.66 (1H, s, C=CH), 4.22 (2H, q,
J 7, CH2O), 3.98 (2H, d, J 1, CH2CO), 3.20 (3H, s, NCH3), 3.15 (3H,
s, NCH3), 1.29 (3H, t, J 7, CH3). δC 169.8, 168.0, 155.8, 130.6, 103.8,
61.6, 37.5, 37.2, 33.9, 14.1. m/z (EI+) 318 (100%, M+•).
Compound 7b: recrystallized from ethyl acetate, 33% yield, mp 223–
224◦C. (Found: C 47.8, H 4.5, N 15.8%, M+• 352.0649. C14H16N4O3S2
•
requires C 47.7, H 4.6, N 15.9%, M+ 352.0658.) δH 7.91 (1H, d, J 9,
3-Diethylamino-6,7-dimethyl-1,1-dioxo-1H-1λ6-thiazolo[3,2-b]-
[1,2,4,6]thiatriazine 5b
ArH), 7.07 (1H, d, J 2, ArH), 7.00 (1H, dd, J 9, 2, ArH), 4.05 (2H, q, J 7,
CH2O), 3.71–3.57 (2H, m, 2 × NCH2), 2.02–1.92 (4H, m, CH2CH2),
1.43 (3H, t, J 7, CH3). δC 167.9, 157.4, 153.9, 128.1, 122.0, 116.6,
115.2, 107.3, 64.3, 47.6, 47.4, 25.2, 24.9, 14.7. m/z (EI+) 352 (100%,
M+•), 219 (52), 192 (44).
Compound 8b: recrystallized from ethanol/chloroform, 4% yield,
mp 241–243◦C (dec). (Found: C 47.6, H 4.4, N 15.7%,•M+• 352.0652.
C14H16N4O3S2 requires C 47.7, H 4.6, N 15.9%, M+ 352.0658.) δH
7.31 (1H, d, J 9, ArH), 7.04 (1H, d, J 2.6, ArH), 6.93 (1H, dd, J 9, 2.6,
ArH), 4.06 (2H, q, J 7, CH2O), 3.48–3.38 (2H, m, 2 × NCH2), 1.98–
1.88 (4H, m, CH2CH2), 1.44 (3H, t, J 7, CH3). δC 165.5, 157.8, 150.9,
126.8, 122.7, 118.3, 113.8, 108.0, 64.4, 50.9, 25.4, 14.7. m/z (EI+) 352
(22%, M+•), 192 (100).
Recrystallized from ethanol, 14% yield, mp 137–138◦C. (Found: C
41.7, H 5.4, N 19.5%, M+• 288.0703. C10H16N4O2S2 requires C 41.7,
H 5.6, N 19.4%, M+• 288.0709.) δH 3.58 (2H, q, J 7, NCH2), 3.52 (2H,
q, J 7, NCH2), 2.44 (3H, s, C=CCH3), 2.19 (3H, s, C=CCH3), 1.21
(3H, t, J 7, CH3), 1.16 (3H, t, J 7, CH3). δC 168.3, 154.6, 128.7, 111.4,
42.5, 42.3, 13.7, 12.9, 12.2, 10.9. m/z (EI+) 288 (100%, M+•), 273 (83),
153 (55).
6,7-Dimethyl-1,1-dioxo-3-pyrrolidin-1-yl-1H-1λ6-thiazolo[3,2-b]-
[1,2,4,6]thiatriazine 5c
Eluted with 20% ethyl acetate in dichloromethane, 41% yield.
Recrystallized•from ethanol, mp 198–199◦C. (Found: C 42.2, H 4.8,
N 19.7%, M+ 286.0547. C10H14N4O2S2 requires C 41.9, H 4.9, N
19.6%, M+• 286.0553.) δH 3.61–3.49 (4H, m, 2 × NCH2), 2.42 (3H, s,
C=CCH3), 2.17 (3H, s, C=CCH3), 1.96–1.86 (4H, m, CH2CH2). δC
168.1, 153.4, 128.7, 111.5, 47.2, 47.1, 25.2, 24.9, 12.2, 10.9. m/z (EI+)
286 (100%, M+•), 153 (63).
General Synthesis Method C
A mixture of the 2-amino-[1,3,4]thiadiazole 9 (3 mmol), the dichloro
compound 1 (3 mmol), sodium carbonate (9 mmol), and DMF (5 mL)
was stirred at room temperature overnight. Ethyl acetate (10 mL) was
stirred in, followed by water (15 mL) and the resulting mixture was
stirred for 1 h. The precipitate was collected by filtration and washed
with water and ethyl acetate. Purification by radial chromatography
and/or recrystallization gave the title compounds.
6,7-Dimethyl-1,1-dioxo-3-piperidin-1-yl-1H-1λ6-thiazolo[3,2-b]-
[1,2,4,6]thiatriazine 5d
The following compounds were prepared by the above procedure:
Recrystallized from ethanol, 44% yield, mp 157–158◦C. (Found: C
44.1, H 5.3, N 18.7%,•M+• 300.0704. C11H16N4O2S2 requires C 44.0,
H 5.4, N 18.7%, M+ 300.0709.) δH 3.77–3.59 (4H, m, 2 × NCH2),
2.38 (3H, s, C=CCH3), 2.14 (3H, s, C=CCH3), 1.57 (6H, br m,
CH2CH2CH2). δC 168.4, 154.0, 128.8, 111.6, 45.6, 45.5, 25.9, 25.6,
24.3, 12.2, 11.0. m/z (EI+) 300 (92%, M+•), 153 (78), 128 (48), 109
(23), 84 (100).
4-Dimethylamino-2,2-dioxo-7-ethyl-2H-2λ6-
[1,3,4]thiadiazolo[2,3-c][1,2,4,6]thiatriazine 10a
Eluted with 0–5% ethyl acetate in dichloromethane and recrystal-
lized from ethyl acetate, 13% yield, mp 170–171◦C. (Found: C 32.0,
H 4.2, N 27.0%, M+• 261.0340. C7H11N5O2S2 requires C 32.2, H 4.2,
•
N 26.8%, M+ 261.0349.) δH 3.25 (6H, s, NMe2), 2.87 (2H, q, J 7,
1,1-Dioxo-3-piperidin-1-yl-1H-1λ6-[1,2,4,6]thiatriazino[3,2-b]-
benzothiazole 7c
CH2), 1.36 (3H, t, J 7, CH3). δC 164.3, 156.2, 147.2, 41.6, 24.9, 11.7.
m/z (EI+) 261 (42%, M+•), 196 (56), 192 (58), 142 (100).
Recrystallized from ethanol, 38% yield, mp 179–179.5◦C. (Found:
4-Dimethylamino-2,2-dioxo-7-ethylthio-2H-2λ6-
[1,3,4]thiadiazolo[2,3-c][1,2,4,6]thiatriazine 10c and
3-Dimethylamino-1,1-dioxo-6-ethylthio-1H-1λ6-
[1,3,4]thiadiazolo[3,2-b][1,2,4,6]thiatriazine 11c
•
C 48.7, H 4.3, N 17.5%, M+ 322.0554. C13H14N4O2S2 requires C
•
48.4, H 4.4, N 17.4%, M+ 322.0553.) δH 8.04–8.02 (1H, m, ArH),
7.61–7.25 (3H, m, ArH), 3.90–3.72 (4H, m, 2 × NCH2), 1.66 (6H, br
m, CH2CH2CH2). δC 168.6, 154.3, 134.6, 127.8, 126.0, 122.0, 120.8,
115.9, 46.0, 45.9, 26.0, 25.6, 24.3. m/z (EI+) 322 (54%, M+•), 175 (92),
84 (100).
Compound 10c: Precipitated in 42% yield. A portion was recrys-
tallized from ethyl acetate, mp 181.5–182.5◦C. (Found: C 28.8, H

N,N-Dialkyl-Nꢀ-Chlorosulfonylchloroformamidines in Heterocyclic Synthesis
897
C4
C6
C6
C3
C5
N5
N4
C5
S2
N2
S2
N2
N5
C1
C2
C1
C7
C2
C7
C8
C3
N1
C4
C8
N3
N3
N1
N4
S1
O1
S1
O2
O1
O2
10d
11d
Fig. 2. ORTEP diagrams of 10d and 11d.
Table 6. Crystal data and structure refinement for 11c, 11d, 10d, 10a, 10e
Parameter
11c
11d
10d
10a
10e
CCDC deposition no.
Empirical formula
Formula weight
Temperature [K]
Wavelength [Å]
Crystal system
Space group
Unit cell dimensions
a [Å]
272515
C7H11N5O2S3
293.39
123(2)
0.71073
272507
C8H13N5O2S2
275.35
123(2)
0.71073
272505
C8H13N5O2S2
275.35
272506
C7H11N5O2S2
261.33
123(2)
0.71073
272516
C10H15N5O2S2
301.39
123(2)
0.71073
123(2)
0.71073
Monoclinic
P21/n
Orthorhombic
Pnma
Orthorhombic
Pna21
Orthorhombic
P212121
Monoclinic
P21/n
17.6684(3)
7.2045(1)
9.4246(2)
90
1199.68(4)
4
1.624
0.616
0.25 × 0.25 × 0.05
3.16 to 28.19
15363
8.4629(1)
18.8711(3)
7.6199(1)
90
1216.93(3)
4
1.503
0.436
0.25 × 0.19 × 0.17
3.76 to 28.19
16784
9.0474(1)
12.3554(2)
10.7739(2)
101.0513(5)
1182.02(3)
4
1.547
0.449
0.28 × 0.13 × 0.12
3.66 to 28.19
22130
8.3113(1)
10.3067(1)
12.9035(2)
90
1105.34(2)
4
1.570
0.476
0.30 × 0.21 × 0.19
3.73 to 28.20
19623
8.3885(1)
12.3165(2)
12.7722(2)
103.8517(5)
1281.21(3)
4
1.562
0.422
0.25 × 0.13 × 0.13
3.69 to 28.21
18680
b [Å]
c [Å]
β [◦]
Volume [Å3]
Z
Density (calc.) [mg m−3
]
Absorption coeff. [mm−1
Crystal size [mm3]
θ range [◦]
]
Reflections collected
Independent reflections
R(int)
1590
0.0480
2923
0.0415
2862
0.0354
2684
0.0399
3121
0.0359
No. of reflections included
1590
2923
2862
2684
3121
in refinement
Final R indices [I > 2σ(I)]
R1
wR2
0.0313
0.0751
0.0258
0.0595
0.0303
0.0709
0.0248
0.0549
0.0314
0.0729
R indices (all data)
R1
wR2
0.0398
0.0795
1.043
0.0303
0.0614
1.050
0.0389
0.0746
1.045
0.0284
0.0562
1.107
0.0415
0.0775
1.061
Goodness-of-fit on F2
Absolute structure parameter
0.02(6)
−0.03(6)
•
3.8, N 23.9%,•M+ 293.0071. C7H11N5O2S3 requires C 28.7, H 3.8,
N 23.9%, M+ 293.0069.) δH 3.25 (3H, s, NMe2), 3.22 (2H, q, J 7,
CH2), 1.47 (3H, t, J 7, CH3). δC 163.9, 152.7, 146.8, 41.5, 27.8, 14.1.
m/z (EI+) 293 (88%, M+•), 173 (53), 140 (38), 103 (100).
3.16 (3H, s, NCH3), 1.47 (3H, t, J 7, CH3). δC 169.2, 155.4, 154.7, 37.9,
37.6, 27.9, 14.0. m/z (EI+) 293 (100%, M+•).
Compound 11c: The organic phase of the mother liquor (from the
original precipitation) was dried and evaporated and the residue was
purified by radial chromatography. Elution with 0–5% ethyl acetate
in dichloromethane afforded the minor isomer 11c in 10% yield.
Recrystallized from ethyl acetate, mp 170.5–171◦C. (Found: C 28.8,
H 3.7, N 23.9%, M+• 293.0068. C7H11N5O2S3 requires C 28.7, H 3.8,
N 23.9%, M+• 293.0069.) δH 3.33 (2H, q, J 7, CH2), 3.20 (3H, s, NCH3),
2,2-Dioxo-7-ethyl-4-piperidin-1-yl-2H-2λ6-[1,3,4]thiadiazolo-
[2,3-c][1,2,4,6]thiatriazine 10e
Recrystallized from ethyl acetate, 29% yield, mp 214.5–215.5◦C.
•
(Found: C 40.1, H 4.9, N 23.4%, M•+ 301.0662. C10H15N5O2S2
requires C 39.9, H 5.0, N 23.2%, M+ 301.0662.) δH 3.70 (4H, m,
2 × NCH2), 2.88 (2H, q, J 7.5, CH2), 1.71 (6H, m, CH2CH2CH2), 1.37

898
G. D. Fallon et al.
(3H, t, J 7, CH3). δC 164.3, 156.4, 146.9, 50.2, 25.4, 24.9, 24.0, 11.6.
m/z (EI+) 236 (49%, M+•), 182 (100).
C8
C7
C9
General Synthesis Method D
C10
A stirred mixture of the 2-amino-[1,3,4]thiadiazole 9 (1.6 mmol) and the
dichloro compound 1 (2 mmol) in DMPU (1 mL) was heated at 80◦C
for 4–5 h. The mixture was cooled and ethyl acetate (5 mL) was stirred
in, followed by water (8 mL) and stirring was continued for 1 h. The
precipitate was collected by filtration and washed with ethyl acetate.
Purification by radial chromatography and/or recrystallization afforded
the title compounds.
C6
C5
C14
N2
C13
C11
C4
N5
N4
C12
C3
O3
C1
The following compounds were prepared by the above procedure:
N3
O1
C2
N1
7-tert-Butyl-4-dimethylamino-2,2-dioxo-2H-2λ6-
[1,3,4]thiadiazolo[2,3-c][1,2,4,6]thiatriazine 10b
S1
Recrystallized from methanol, 31% yield, mp 209–210◦C. (Found:
C 37.2, H 5.1, N 24.3%, M+• 289.0656. C9H15N5O2S2 requires C 37.4,
O2
•
H 5.2, N 24.2%, M+ 289.0662). δH 3.27 (6H, s, NMe2), 1.40 (9H, s,
13d
Fig. 3. ORTEP diagram of 13d.
Table 7. Crystal data and structure refinement for 13a and 13d
But). δC 164.4, 164.1, 147.2, 41.7, 37.1, 29.3. m/z (EI+) 289 (40%,
M+•), 224 (82), 220 (60), 170 (100).
4-Diethylamino-2,2-dioxo-7-methyl-2H-2λ6-
[1,3,4]thiadiazolo[2,3-c][1,2,4,6]thiatriazine 10d and
3-Diethylamino-1,1-dioxo-6-methyl-1H-1λ6-[1,3,4]thiadiazolo-
[3,2-b][1,2,4,6]thiatriazine 11d
Parameter
13a
13d
CCDC deposition number
Empirical formula
Formula weight
Temperature [K]
Wavelength [Å]
Crystal system
Space group
Unit cell dimensions
a [Å]
272513
272514
C14H17N5O3S
335.39
Compound 10d: Precipitated in 23% yield. A portion was recrys-
tallized from ethyl acetate, mp 220.5–221.5◦C. (Found: C 34.9, H 4.6,
N 25.6%. C8H13N5O2S2 requires C 34.9, H 4.8, N 25.4%). δH 3.62
(4H, q, J 7, 2 × NCH2), 2.56 (3H, s, CH3), 1.30 (6H, t, J 7, 2 × CH3).
δC 164.4, 150.3, 145.8, 46.1, 17.1, 13.1. m/z (EI+) 275 (2%, M+•), 260
(10), 196 (100).
Compound 11d: The organic phase of the filtrate (from the original
precipitation) was dried and evaporated and the residue was purified
by radial chromatography. Elution with dichloromethane afforded the
minor isomer 11d in 4% yield. Recrystallized from ethyl acetate, mp
167–168◦C. (Found: C 35.0, H 4.6, N 25.6%. C8H13N5O2S2 requires
C 34.9, H 4.8, N 25.4%). δH 3.60 (2H, q, J 7, NCH2), 3.55 (2H, q, J 7,
NCH2), 2.61 (3H, s, CH3), 1.23 (3H, t, J 7, CH3), 1.19 (3H, t, J 7, CH3).
δC 169.5, 154.6, 152.8, 43.3, 42.9, 16.7, 13.6, 12.7. m/z (EI+) 275 (38%,
M+•), 260 (100).
C12H13N5O3S
307.33
123(2)
123(2)
0.71073
Monoclinic
P21
0.71073
Monoclinic
P21
7.4451(2)
10.3251(2)
8.6694(2)
94.7038(9)
664.18(3)
2
8.4322(1)
9.1411(1)
10.6305(2)
104.9386(6)
791.70(2)
2
b [Å]
c [Å]
β [◦]
Volume [Å3]
Z
Density (calc.) [mg m−3
]
1.537
0.263
1.407
0.227
Absorption coeff. [mm−1
Crystal size [mm3]
θ range [◦]
]
0.3 × 0.25 × 0.18 0.31 × 0.22 × 0.08
2,2-Dioxo-7-ethylthio-4-piperidin-1-yl-2H-2λ6-
[1,3,4]thiadiazolo[2,3-c][1,2,4,6]thiatriazine 10f
3.76 to 28.22
9745
3.35 to 28.21
11744
3840
0.0283
3840
Reflections collected
Independent reflections
R(int)
Recrystallized from ethyl acetate, 29% yield, mp 151–152◦C.
3199
0.0334
•
(Found: C 36.1, H 4.4, N 21.0%, M•+ 333.0373. C10H15N5O2S3
requires C 36.0, H 4.5, N 21.0%, M+ 333.0382). δH 3.67 (4H, m,
2 × NCH2), 3.22 (2H, q, J 7, CH2), 1.71 (6H, m, CH2CH2CH2), 1.48
(3H, t, J 7, CH3). δC 163.9, 153.0, 146.6, 50.1, 27.7, 25.5, 24.0, 14.2.
m/z (EI+) 333 (5%, M+•), 268 (38), 211 (28), 182 (100).
No. of reflections included 3199
in refinement
Final R indices [I > 2σ(I)]
R1
wR2
0.0313
0.0718
0.0279
0.0691
2-Amino-[1,3,4]oxadiazoles 12a, 12b, 12c, 12d
R indices (all data)
R1
2-Amino-5-benzyl[1,3,4]oxadiazole 12a,[18–20] 2-amino-5-(4-tert-
butylphenyl)[1,3,4]oxadiazole 12b,[21] 2-amino-5-(2-thienyl)[1,3,4]-
oxadiazole 12d,[21,22] and 2-amino-5-phenyl[1,3,4]oxadiazole
12e[18–20,23] were prepared by slight modification of a literature
procedure.[20,21] Hence, cyanogen bromide (5.0 M in acetonitrile,
6 mL, 30 mmol) was added portionwise to a stirred suspension of the
hydrazide (30 mmol) and potassium bicarbonate (3.0 g, 30 mmol) in
water (100 mL). More water (35 mL) was added to wash the froth
back into the bulk mixture and stirring was continued overnight. More
potassium bicarbonate (1.5 g, 15 mmol) and cyanogen bromide solution
(3 mL, 15 mmol) were added and the resulting mixture again stirred
overnight. The mixture was filtered and the white solid was washed on
the filter with water and then air dried. Drying the solid over phospho-
rus pentoxide in a vacuum oven at 110◦C overnight provided the title
compounds, which were used without further purification.
0.0374
0.0747
1.037
0.0319
0.0711
1.097
−0.04(5)
wR2
Goodness-of-fit on F2
Absolute structure
parameter
0.03(6)
[D6]DMSO) 163.9, 158.7, 134.4, 128.61, 128.59, 127.1, 31.7. m/z (EI+)
175 (100%, M+•), 91 (97).
Compound 12b: δH (CDCl3 + 1 drop TFA) 9.89 (2H, br s, NH2),
7.88–7.80(2H, m,ArH), 7.60–7.52(2H, m,ArH), 1.36(9H, s, C(CH3)3).
Compound 12d: δH ([D6]DMSO) 7.73 (1H, dd, J 5, 1.2, ArH), 7.51
(1H, dd, J 3.7, 1.2, ArH), 7.30 (2H, br s, NH2), 7.18 (1H, dd, J 5, 3.7,
ArH). δC ([D6]DMSO) 163.3, 153.7, 128.8, 128.2, 127.2, 125.6. m/z
(EI+) 167 (100%, M+•), 124 (42), 111 (26).
Compound 12a: δH (CDCl3 + ∼10% [D6]DMSO) 7.14–6.96 (5H,
Compound 12e: δH ([D6]DMSO) 7.84–7.74 (2H, m, ArH), 7.55–
7.45 (3H, m, ArH), 7.29 (2H, br s, NH2). δC ([D6]DMSO) 163.8, 157.3,
m,ArH), 6.05 (2H, br s, NH2), 3.78 (2H, s, CH2Ph). δC (CDCl3 + ∼10%

N,N-Dialkyl-Nꢀ-Chlorosulfonylchloroformamidines in Heterocyclic Synthesis
899
130.3, 129.1, 124.9, 124.3. m/z (EI+) 161 (100%, M+•), 118 (75), 105
(40), 91 (30), 77 (52).
Compound 14d: The organic phase from the filtrate (from the
original precipitation) was dried and evaporated and the residue was
purified by radial chromatography. Elution with dichloromethane/
light petroleum (2/1) afforded the minor isomer 14d in 5% yield.
Recrystallized from ethyl acetate, mp 117–118◦C. (Found: C 50.3,
H 5.3, N 20.8%, M+• 335.1046. C14H17N5O3S requires C 50.1, H 5.1,
N 20.9%, M+• 335.1047). δH 7.41–7.29 (5H, m, Ph), 4.09 (2H, s, CH2),
3.57 (2H, q, J 7, NCH2), 3.55 (2H, q, J 7, NCH2), 1.23 (3H, t, J 7,
CH3), 1.18 (3H, t, J 7, CH3). δC 159.8, 157.6, 155.3, 131.2, 129.2,
129.0, 128.3, 43.6, 43.1, 32.0, 13.5, 12.6. m/z (EI+) 335 (16%, M+•),
320 (100).
(E)-2-Amino-5-(1-methyl-2-phenylvinyl)[1,3,4]oxadiazole 12c
A
stirred mixture of α-methyl-trans-cinnamaldehyde (2.92 g,
20 mmol), sodium acetate trihydrate (3.0 g, 22 mmol), semicarbazide
hydrochloride (2.2 g, 22 mmol), DMPU (6 mL), and water (40 mL) was
heated at 70◦C for 4 h, and then diluted with water (60 mL), cooled to
room temperature, and neutralized with sodium carbonate (12 mmol).
Sodium iodide (30 mmol) was added followed by iodine (30 mmol) (in
0.5 g portions) and the resulting mixture was stirred overnight at room
temperature and then at 90◦C for 3 h. Sodium sulfite (0.5 g) was added
to the cooled mixture and stirring continued at room temperature for 3 h.
The mixture was filtered and the collected solid was washed with water
to give the title compound (2.4 g, 21%) as a light brown powder, which
was used without further purification.A portion was recrystallized from
ethanol to give colourless needles, mp >260◦C. (Found: C 65.4, H 5.6, N
21.0%. C11H11N3O requires C 65.7, H 5.5, N 20.9%). δH ([D6]DMSO)
7.28–7.46 (5H, m, Ph), 7.17 (2H, s, NH2), 7.08 (1H, s, C=CH), 2.21
(3H, s, CH3). δC ([D6]DMSO) 163.6, 159.7, 135.5, 129.4, 129.3, 128.5,
127.8, 121.4, 14.0. m/z (EI+) 201 (20%, M+•), 200 (100).
4-Diethylamino-2,2-dioxo-7-thien-2-yl-2H-2λ6-
[1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine 13e
Precipitated in 48% yield. A portion was recrystallized from ethyl
acetate/chloroform (1/1), mp 232–233◦C. (Found: C 40.4, H 4.1, N
21.4%, M+• 327.0450. C11H13N5O3S2 requires C 40.4, H 4.0, N 21.4%,
•
M+ 327.0454). δH 7.86–7.82 (1H, m, ArH), 7.76–7.72 (1H, m, ArH),
7.29–7.23 (1H, m, ArH), 3.74 (4H, q, J 7, 2 × NCH2), 1.35 (6H, t, J 7,
2 × CH3). δC 153.5, 151.3, 143.0, 133.4, 133.2, 128.9, 121.6, 45.7, 13.2.
m/z (EI+) 327 (11%, M+•), 312 (12), 248 (74), 193 (88), 165 (38), 137
(52), 111 (100).
General Synthesis Method E
2,2-Dioxo-7-phenyl-4-piperidin-1-yl-2H-2λ6-
[1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine 13f
A stirred mixture of the 2-amino-[1,3,4]oxadiazole 12 (2 mmol) and the
dichloro compound 1 (2.4 mmol) in DMPU (3 mL) was heated at 80–
90◦C for 2 h. The mixture was cooled and ethyl acetate (10 mL) was
stirred in, followed by water (10 mL). The resulting mixture was stirred
vigorously for 1 h. The aqueous layer was carefully removed using a
pipette (without removing any precipitate) and more water (10 mL) was
added. The mixture was stirred vigorously for a further 1 h and the
precipitate was collected by filtration. The solid was washed with ethyl
acetate and purified by recrystallization to afford the title compounds.
The following compounds were prepared by the above procedure:
Precipitated in 85% yield.† An analytical sample was recrystallized
from ethanol, mp 256–257◦C (dec.). (Found: C 50.4, H 4.4, N 20.9%,
•
•
M+ 333.0885. C14H15N5O3S requires C 50.4, H 4.5, N 21.0%, M+
333.0890). δH 8.01–7.93 (2H, m, ArH), 7.74–7.53 (3H, m, ArH), 3.95
(4H, m, 2 × NCH2), 1.76 (6H, m, CH2CH2CH2). δC 154.5, 154.1, 143.4,
134.0, 129.5, 127.3, 120.7, 49.3, 25.5, 24.0. m/z (EI+) 333 (5%, M+•),
269 (24), 268 (62), 139 (46), 109 (94), 105 (100).
7-(4-tert-Butylphenyl)-2,2-dioxo-4-piperidin-1- yl-2H-2λ6-
[1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine 13g
7-Benzyl-4-dimethylamino-2,2-dioxo-2H-2λ6-
[1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine 13a
Precipitated in 72% yield. A portion was recrystallized from ethyl
acetate, mp 246–247◦C. (Found: C 55.3, H 6.2, N 17.9%, M+• 389.1507.
C18H23N5O3S requires C 55.5, H 6.0, N 18.0%, M+• 389.1516). δH 7.89
(2H, dt, J 9, 2,ArH), 7.59 (2H, dt, J 9, 2,ArH), 3.94 (4H, m, 2 × NCH2),
1.76 (6H, m, CH2CH2CH2), 1.37 (9H, s, But). δC 158.1, 154.7, 154.2,
143.5, 127.2, 126.5, 117.7, 49.2, 35.4, 31.0, 30.9, 25.5, 24.0. m/z (EI+)
389 (7%, M+•), 324 (49), 172 (100).
Precipitated in 80% yield.∗ A portion was recrystallized from
met•hanol, mp 212–213◦C (dec.). (Found: C 46.8, H 4.4, N 22.6%,
•
M+ 307.0734. C12H13N5O3S requires C 46.9, H 4.3, N 22.8%, M+
307.0734). δH 7.45–7.25 (5H, m, Ph), 4.06 (2H, s, CH2), 3.30 (6H, s,
NMe2). δC 156.7, 155.3, 145.0, 132.6, 129.7, 129.1, 128.1, 40.7, 31.2.
m/z (EI+) 307 (50%, M+•), 242 (41), 188 (100).
7-(4-tert-Butylphenyl)-4-dimethylamino-2,2-dioxo-2H-2λ6-
[1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine 13b
(E)-4-Dimethylamino-2,2-dioxo-7-(1-methyl-2-phenylvinyl)-2H-
2λ6-[1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine 13c
Precipitated in 23% yield. A portion was recrystallized from
met•hanol, mp 278.5–279.5◦C (dec.). (Found: C 51.4, H 5.7, N 19.9%,
A stirred mixture of the 2-amino-[1,3,4]oxadiazole 12c (0.67 g,
3.33 mmol) and the dichloro compound 1a (0.89 g, 4.33 mmol) in
DMPU (3 mL) was heated at 80–90◦C for 1 h. The mixture was cooled
and diluted slowly with 2 N HCl (8 mL). The precipitate was collected
and washed with 1 N HCl and isopropyl alcohol, and then recrystallized
from methanol/chloroform (∼2/1) to afford the title compound (0.31 g,
27%) as colourless crystals, mp 256–257.5◦C (dec.). (Found: C 50.2,
H 4.7, N 20.8%, M+• 333.0885. C14H15N5O3S requires C 50.4, H 4.5,
•
M+ 349.1198. C15H19N5O3S requires C 51.6, H 5.5, N 20.0%, M+
349.1203). δH 7.88 (2H, dt, J 9, 2, ArH), 7.58 (2H, dt, J 9, 2, ArH), 3.42
(6H, s, NMe2), 1.37 (9H, s, But). δC 158.1, 154.6, 154.0, 144.3, 127.2,
126.5, 117.7, 40.9, 35.4, 31.0. m/z (EI+) 349 (32%, M+•), 229 (20),
172 (100).
•
N 21.0%, M+ 333.0890). δH 7.58 (1H, m, ArH), 7.49–7.41 (5H, m,
7-Benzyl-4-diethylamino-2,2-dioxo-2H-2λ6-
[1,3,4]oxadiazolo[2,3-c][1,2,4,6]thiatriazine 13d and
6-Benzyl-3-diethylamino-1,1-dioxo-1H-1λ6-
[1,3,4]oxadiazolo[3,2-b][1,2,4,6]thiatriazine 14d
ArH), 3.39 (6H, m, NMe2), 2.30 (3H, d, J 1.4, CH3). δC 156.4, 153.8,
144.1, 139.8, 134.2, 130.0, 129.7, 128.8, 118.0, 40.8, 13.5. m/z (EI+)
333 (75%, M+•), 263 (64), 262 (46), 129 (100).
Compound 13d: Precipitated in 37% yield. A portion was recrystal-
lized from ethyl acetate, mp 190.5–191.5◦C. (Found: C 50.1, H 5.3, N
20.9%, M+• 335.1035. C14H17N5O3S requires C 50.1, H 5.1, N 20.9%,
M+• 335.1047). δH 7.45–7.25 (5H, m, Ph), 4.06 (2H, s, CH2), 3.65 (4H,
q, J 7, 2 × NCH2), 1.25 (6H, t, J 7, 2 × CH3). δC 157.1, 154.4, 142.3,
130.8, 129.09, 129.08, 128.3, 45.6, 32.0, 13.1. m/z (EI+) 335 (4%, M+•),
334 (6), 256 (100).
Acknowledgments
We thank Roger Mulder for assistance with NMR spec-
troscopy and E. I. DuPont de Nemours and Co., Agricultural
Products Department, for the biological screening of these
compounds.
∗Using freshly prepared dichloro compound 1a.
†Using freshly prepared dichloro compound 1d.

900
G. D. Fallon et al.
References
[13] J. S. McFadyen, T. S. Stevens, J. Chem. Soc. 1936, 584.
doi:10.1039/JR9360000584
[14] M. Knollmüller, R. Fauß, Monatsh. Chem. 1985, 116, 1027.
doi:10.1007/BF00809195
[15] G. Kornis, in Comprehensive Heterocyclic Chemistry (Eds
A. R. Katritzky, C. W. Rees) 1984, Vol. 6, p. 545 (Pergamon:
Oxford).
[16] G. M. Sheldrick, SHELXS-97 1997 (University of Göttingen:
Göttingen).
[17] G. M. Sheldrick, SHELXL-97 1997 (University of Göttingen:
Göttingen).
[18] A. P. Swain, US Pat. 2883391 1957 (McNeil Laboratories Inc.).
[19] H. Gehlen, G. Blankenstein, Justus Liebigs Ann. Chem. 1960,
638, 136.
[20] H. Gehlen, Justus Liebigs Ann. Chem. 1949, 563, 185.
[21] B. Pradhan, P. K. Misro, A. K. Padhy, J. Ind. Chem. Soc. 2002,
79, 898.
[22] H. Gehlen, P. Demin, K.-H. Uteg, Arch. Pharm. Ber. Dtsch.
Pharm. Ges. 1970, 303, 310.
[1] A. K. Ghose,V. N.Viswanadhan, J. J.Wendoloski, J. Comb. Chem.
1999, 1, 55. doi:10.1021/CC9800071
[2] A. R. Katritzky, A. F. Pozharskii, Handbook of Heterocyclic
Chemistry 2003 (Pergamon: Oxford).
[3] R. Chinchilla, C. Najera, M. Yus, Chem. Rev. 2004, 104, 2667.
doi:10.1021/CR020101A
[4] S. K. Bur, A. Padwa, Chem. Rev. 2004, 104, 2401.
doi:10.1021/CR020090L
[5] N. Schindler, Chem. Ber. 1973, 106, 56.
[6] L. N. Markovskii, Y. G. Shermolovich, V. I. Shevchenko, J. Org.
Chem. USSR (Engl. Transl.) 1973, 9, 644.
[7] L. N. Markovskii, Y. G. Shermolovich, V. I. Shevchenko, J. Org.
Chem. USSR (Engl. Transl.) 1974, 10, 492.
[8] M. Knollmüller, P. Kosma, Monatsh. Chem. 1985, 116, 1321.
doi:10.1007/BF00811103
[9] H. Schröder, E. Fischer, M. Michalik, J. Prakt. Chem. 1988, 330,
900. doi:10.1002/PRAC.19883300609
[10] G. D. Fallon, S. Jahangiri, A. J. Liepa, R. C. J. Woodgate, Aust. J.
Chem. 2005, 58, 332. doi:10.1071/CH04295
[11] R. Barone, M. Chanon, R. Gallo, inThe Chemistry of Heterocyclic
Compounds (EdsA. Weissberger, E. C. Taylor) 1979, Vol. 34, p. 9
(Wiley InterScience: New York, NY).
[23] G. Kaupp, J. Schmeyers, J. Boy, Chem. Eur. J. 1998,
4, 2467. doi:10.1002/(SICI)1521-3765(19981204)4:12<2467::
AID-CHEM2467>3.0.CO;2-D
[12] J. Metzger, in Comprehensive Heterocyclic Chemistry (Eds
A. R. Katritzky, C. W. Rees) 1984, Vol. 6, p. 235 (Pergamon:
Oxford).