N,N-dialkyl-N′-chlorosulfonyl chloroformamidines in heterocyclic synthesis. VI the preparation of some fused [1,4,2,6]dithiadiazine dioxides

Article abstract of DOI:10.1071/CH08059

N,N-Dialkyl-N′-chlorosulfonylchloroformamidines 1 were treated with 2-mercaptobenzimidazoles 2 to give [1,4,2,6]dithiadiazino[2,3-a]benzimidazole 1,1-dioxides 3. 3-Mercapto[1,2,4]triazoles 5 afforded [1,2,4]triazolo[2,3-b][1, 4,2,6]dithiadiazine 1,1-dioxides 6 and [1,2,4]triazolo[4,3-b][1,4,2,6] dithiadiazine 1,1-dioxides 7. These products are derivatives of new or very rare heterocycles. CSIRO 2008.

Full text of DOI:10.1071/CH08059

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2008, 61, 332–341
www.publish.csiro.au/journals/ajc
N,N-Dialkyl-Nꢀ-Chlorosulfonyl Chloroformamidines
in Heterocyclic Synthesis. VI The Preparation of Some
Fused [1,4,2,6]Dithiadiazine Dioxides
Teresa Cablewski,A Craig L. Francis,A,B and Andris J. LiepaA
ACSIRO Molecular and Health Technologies, Clayton VIC 3168, Australia.
BCorresponding author. Email: craig.francis@csiro.au
N,N-Dialkyl-Nꢀ-chlorosulfonylchloroformamidines 1 were treated with 2-mercaptobenzimidazoles 2 to give [1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 1,1-dioxides 3. 3-Mercapto[1,2,4]triazoles 5 afforded [1,2,4]triazolo[2,3-b][1,4,2,6]
dithiadiazine 1,1-dioxides 6 and [1,2,4]triazolo[4,3-b][1,4,2,6]dithiadiazine 1,1-dioxides 7. These products are derivatives
of new or very rare heterocycles.
Manuscript received: 14 February 2008.
Final version: 11 April 2008.
Introduction
R1R2N
R1R2N
Cl
We have been exploring the application of N,N-dialkyl Nꢀ-
chlorosulfonylchloroformamidines 1[1–5] to the synthesis of
novel, low molecular weight, heterocyclic compounds.[6–10]
In Part I[6] of this series, we reported regioselective reac-
tions between 1 and two representative 1,2-dinucleophilic sys-
tems (hydrazines and hydroxamic acids) to give uncommon
five-membered heterocycles ([1,2,3,5]thiatriazole dioxides and
[1,3,2,4]oxathiadiazole dioxides). In Parts II,[7] III,[8] and V,[10]
we detailed reactions of dichlorides 1 with six classes of 2-
amino-1-azaheterocyclic compounds, as representative N–C–N
1,3-dinucleophilic species, derived from readily available thia-
zole, [1,3,4]thiadiazole, [1,3,4]oxadiazole, pyridine, pyridazine,
and benzimidazole systems. These species provided a variety
of novel, or uncommon, ring-fused [1,2,4,6]thiatriazine diox-
ides. In Part IV,[9] we described regioselective reactions of
dichlorides 1 with some 4-hydroxy-2-pyrone derivatives, as a
representative class of C–C–O 1,3-dinucleophilic species, to
form the previously unknown pyrano[3,4-e][1,4,3]oxathiazine
ring system.
SO2Cl2
Me2N
Et2N
1a
1b
R1R2N
N
NSO2Cl
1c
1d
N
1
N
BnMeN 1e
Scheme 1.
dioxides 3 were selectively precipitated from the reaction mix-
ture in high purity and generally in good yield by the addition of
ethyl acetate and water and adjustment to pH 3.The desired prod-
ucts 3 appeared at the interface between the organic and aqueous
phases and were isolated by simple filtration. In some instances,
the addition of diethyl ether aided the precipitation process.
However, with 3b and 3l/3m the compounds were too soluble
in ethyl acetate/diethyl ether; in these cases the products were
isolated by chromatography.
The presence of Hünig’s base during the reaction and the
adjustment of the pH during the precipitation process were
not necessary but its inclusion resulted in slightly increased
yields. In some cases, after the initial precipitation procedure,
more of the product 3 was obtained from the mother liquors by
chromatographic purification of the residue.
To further demonstrate the versatility of dichlorides 1 in the
synthesis of novel or uncommon heterocyclic ring systems, we
now report results of reactions of 1 with some 2-mercapto-1H-
azaheterocyclic compounds, which embody readily available
S–C–N 1,3-dinucleophilic systems.
The examples of the new heterocyclic system 3 described
above were stable, colourless, crystalline solids and were un-
affected by recrystallization from alcohols.
Results and Discussion
The dichlorides 1a–e were readily prepared[1,2,6] from sulfuryl
chloride and the corresponding dialkyl cyanamide (Scheme 1).
Reaction of 1 with 2-mercaptobenzimidazoles 2 in 1,3-
The dichlorides 1, being ambident dielectrophiles, have
two reactive sites and cyclization reactions with dinucleophilic
2-mercapto-1H-azaheterocyclic compounds such as 2 could, in
principle, result in two isomeric ring systems being formed.
However, the possible regioisomeric products 4 (Fig. 1) were
not isolated during the course of chromatographic purification.
In the mercaptobenzimidazoles 2 where R3 and R4 are differ-
ent (such as with 2d and 2e), another source of regioisomerism
dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone
(dimethyl-
propylene urea, DMPU) in the presence of Hünig’s base
provided derivatives of the hitherto unreported ring sys-
tem [1,4,2,6]dithiadiazino[2,3-a]benzimidazole 3 (Scheme 2,
Table 1). Often the [1,4,2,6]dithiadiazino[2,3-a]benzimidazole
© CSIRO 2008
10.1071/CH08059
0004-9425/08/050332

Preparation of Some Fused [1,4,2,6]Dithiadiazine Dioxides
333
R2
N
R2
R3
R4
S
S
Pri2 NEt
DMPU
N
N
R1
N
Cl
R1
HS
ꢀ
N
N
N
H
NSO2Cl
R3
O
O
1
2
R4
3
Scheme 2.
Table 1. Synthesis of the [1,4,2,6]dithiadiazino[2,3-a]benzimidazole
1,1-dioxides 3
S4
N5
N3
R1R2N
R3
R4
Product
Yield [%]
C3
N2
C6
C7
Me2N (1a)
Et2N (1b)
H
H
H (2a)
H (2a)
3a
3b
79
27
N10
H
H (2a)
3c
50
S1
O1
N
(1c)
C8
O2
C9
H
H (2a)
3d
52
N
(1d)
CI1
BnMeN (1e)
Me2N (1a)
Et2N (1b)
Et2N (1b)
H
Cl
Cl
H (2a)
Cl (2b)
Cl (2b)
3e
3f
3g
3h
27
76
59
43
3k
benzo fused (2c)
benzo fused (2c)
3i
76
N
(1d)
S4
Me2N (1a)
Et2N (1b)
Cl
H (2d)
H (2e)
3j (R3 = Cl, R4 = H)
3k (R3 = H, R4 = Cl)
3l (R3 = H, R4 = OMe)
3m (R3 = OMe, R4 = H)
19
N5
N3
18A
11
OMe
C6
C3
13
C7
OMe H (2e)
3n (R3 = H, R4 = OMe)
11
13
N3
N10
3o (R3 = OMe, R4 = H)
N
S1
O3
(1d)
O2
C8
C9
O1
A11% starting mercaptobenzimidazole 2d recovered.
R3
R4
3m
Fig. 2. ORTEP diagrams of 3k and 3m.
R2
N
by X-ray crystallography and therefore the structure of 3j could
be assigned. X-ray crystallography was also used to verify the
structure of 3m, hence the structure of 3l was known. The 1H
NMR chemical shifts of the three aromatic hydrogen atoms in 3l
and 3n were almost identical as were those for 3m and 3o and
this allowed assignment of structures for 3n and 3o.
N
N
R1
N
S
S
O
O
4
In the 1H NMR spectra of compounds 3, differentiation
between the resonances attributable to the methyl or methylene
groups flanking the nitrogen atom of the dialkylamino sub-
stituent was observed. In the case of the (N-methyl)benzylamino
derivative 3e, which is not symmetrical about the exocyclic
C–N bond, two sets of N-methyl and benzylic methylene sig-
nals were observed in the 1H NMR spectrum recorded in either
CDCl3 or [D6]DMSO at 25◦C. When the spectrum of 3e was
recorded in [D6]DMSO at 100◦C, both pairs of resonances coa-
lesced to single signals. On cooling to 20◦C, the resonances
reverted to twin signals. The 13C NMR spectra in CDCl3 and
[D6]DMSO also contained additional resonances. All of these
observations suggest that compounds 3 exist as two rotamers
that interconvert by slow (on the NMR timescale) rotation of the
amino substituent. This phenomenon was noted in our earlier
Fig. 1. Possible regioisomeric products.
exists. Inreactionsinvolvingthesetwounsymmetricalmercapto-
benzimidazoles, similar quantities of the two possible isomers
were formed (see Table 1, 3j–o). The separation of these pairs
of isomers was difficult but in each case chromatography using
long retention times yielded pure samples of each isomer, as well
as a mixed fraction (Table 1).
Spectroscopic studies alone did not allow convincing struc-
tural assignments and consequently unequivocal determination
of structures 3 was based on X-ray crystallographic analyses
of representative compounds (Fig. 2) and aided by consistent
trends in 1H NMR chemical shifts of the three aromatic hydrogen
atoms in compounds 3l–o. The structure of 3k was confirmed

334
T. Cablewski, C. L. Francis, and A. J. Liepa
R2
R2
N
R2
N
N
S
S
N
R1
Cl
N
N
Pri2 NEt
DMPU
R1
N
N
R1
R3
ꢀ
N
ꢀ
R3
N
N
N
N
HS
N
Cl
N
H
S
S
S
R3
O
O
O
O
O
O
7
5
6
1
Scheme 3.
Table 2. Synthesis of the [1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine
1,1-dioxides
6
and [1,2,4]triazolo[4,3-b][1,4,2,6]dithiadiazine 1,1-
dioxides 7
S4
N5
N7
R1R2N
R3
Product(s)
Yield(s) [%]
N3
C3
N2
H (5a)
6a(+7a)
6b(+7b)
30 (+21)
15 (+23)
C6
N
(1d)
N8
Et2N (1b)
Pri (5b)
S1
O2
O1
But (5c)
Ph (5d)
6c
63
15
N
(1c)
6a
Et2N (1b)
6d
Ph (5d)
6e
49
N
(1d)
Me2N (1a)
Et2N (1b)
4-But-Ph (5e)
4-But-Ph (5e)
6f
53
29 (+10)
6g(+7g)
S4
4-But-Ph (5e)
6h
6i
43
47
N5
N
(1c)
N3
C3
4-But-Ph (5e)
N6
N
(1d)
N2
Me2N (1a)
Et2N (1b)
4-Py (5f)
4-Py (5f)
6j
6k
65
35
N8
C7
S1
O1
4-Py (5f)
4-Py (5f)
6l
54
35
N
(1c)
O2
7a
BnMeN (1e)
6m
work with the structurally related [1,2,4,6]thiatriazines[8,10] and
[1,4,3]oxathiazines.[9]
S4
Having efficiently constructed ring-fused [1,4,2,6]dithiadi-
azines 3 from dichlorides 1 and 2-mercaptobenzimidazoles 2, we
envisagedananalogousreactionwith3-mercapto[1,2,4]triazoles
5. Indeed, such a reaction gave 3-dialkylamino-1,1-dioxo-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazines 6 and, on occasion,
the isomeric 3-dialkylamino-1,1-dioxo-1λ6-[1,2,4]triazolo[4,3-
b][1,4,2,6]dithiadiazines 7 (Scheme 3, Table 2). Compounds 6
represent derivatives of a unique heterocyclic system and there
is only one report[11] of the ring system of 7.
N5
N7
N3
C6
C3
N6
N2
N8
S1
O1
O1i
In approximately half of the reactions, the major product,
the [1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine dioxide 6, was
obtained by direct precipitation from the reaction mixture, gener-
ally in quite high purity. In the other cases, chromatography was
required. The yields ranged from moderate to good and longer
reaction times did not improve the yields. For example, with
the preparation of 6g and 7g, the standard reaction time of 4 h
afforded atotalyieldof39%, whereas another experiment lasting
16 h resulted in a 37% total yield with a similar isomer ratio. The
reaction proceeded in the absence of Hünig’s base but in lower
yield, and higher temperature and longer reaction time were
6j (atoms denoted i generated by symmetry operator x, 1/2 ꢁ y, z)
Fig. 3. ORTEP diagrams of 6a, 7a, and 6j.
required. For example, 6e was prepared in 19% yield by heating
a mixture of 5d and 1d in DMPU solution at 80◦C for 24 h.
The examples of the new heterocyclic system 6 described
above were all stable, colourless, crystalline solids and they
were unaffected by recrystallization from alcohols.The isomeric
[1,2,4]triazolo[4,3-b][1,4,2,6] dithiadiazine dioxides 7a, 7b, and

Preparation of Some Fused [1,4,2,6]Dithiadiazine Dioxides
335
7g were stable solids, but showed signs of decomposition in
solution during recrystallization trials.
This suggests an order of nucleophilicity for these mercaptotria-
zoles of S > N2 > N4. Our observations in the current work are
consistent with the above findings and this raises the possibility
that the previously reported[11] compounds possessing the ring
system of 7 may actually contain the isomeric ring system of 6.
Interestingly, during 1H NMR spectroscopic analysis of pure
compound 7a in CDCl3, we noted that a sample that had been
stored in CDCl3 solution at room temperature for several hours
then showed the presence of ∼40% of isomer 6a. The 13C NMR
spectrum also showed additional signals corresponding to 6a.
After a further 4 days, the sample contained more than 90% of
Assignment of structures for dithiadiazines 6 and 7 was based
on X-ray crystallographic analyses of representative compounds
(Fig. 3, Table 4) and relative behaviour during TLC. It was
observed that the [1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine
dioxides 6 were significantly more mobile than the isomeric
[1,2,4]triazolo[4,3-b][1,4,2,6]dithiadiazine dioxides 7 during
TLC using minor proportions of methanol or ethyl acetate in
dichloromethane. Interestingly, duringTLC with a 1:1 mixture of
ethyl acetate/petroleum spirit as developing solvent, the relative
mobilities were reversed.
1
isomer 6a (by H NMR). Similarly, an NMR sample of com-
In principle, reaction of the dielectrophilic compounds 1
with mercaptotriazoles 5 could result in the formation of two
additional isomeric ring systems. However, during the course
of chromatographic purification, the possible regioisomeric
products 8 or 9 (Fig. 4) were not isolated.
The [1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine dioxides 6,
which result from bonding of the sulfur atom of 5 to the amidine
carbon atom of 1 and N2 reacting with the sulfonyl chloride moi-
ety, were usually the major products. In some cases, the isomeric
[1,2,4]triazolo[4,3-b][1,4,2,6]dithiadiazine dioxides 7, formed
by reaction of N4 with the sulfonyl chloride moiety of 1, were
isolated in significant proportion.
pound 7b that had been stored in CDCl3 at room temperature
for 1 week had completely converted to isomer 6b.TLC analysis
of each of these samples after a week in CDCl3 confirmed that
they had completely converted to the corresponding isomers 6a
and 6b. These results suggested an isomerization catalyzed by
the trace of HCl often found in CDCl3.
To test this hypothesis, a drop of concentrated hydrochloric
acid was added to a small sample of 7a in chloroform. The
sample was shaken vigorously, left to stand for a few minutes,
1
and then dried and evaporated. Subsequent H NMR analysis
of the residue in CDCl3 showed none of compound 7a and a
complete conversion into isomer 6a. A possible mechanism for
this interconversion is outlined in Scheme 4.
The proposed mechanism involves HCl-induced cleavage of
the triazole–N4–SO2 bond followed by rotation of the triazole
group and subsequent attachment of the triazole–N2 to the SO2
moiety.
We have reported[6–8] that the chlorosubstituted amidine car-
bon atom of 1 seems to be the more reactive electrophilic
site, at least towards nitrogenous nucleophiles. Others have
reported that 5-phenyl-3-mercapto[1,2,4]triazoles react with
ambident electrophilic reagents, such as α-haloketones and
2-chloromethyloxirane first via the mercapto group and subse-
quently at N2, rather than N4, to afford bicyclic products.[12,13]
As with compounds 3 described earlier, the 1H NMR spectra
of compounds 6 displayed differentiation between the reso-
nances attributable to the methyl or methylene groups flank-
ing the nitrogen atom of the dialkylamino substituent. The
1H NMR spectrum of 6m (bearing the non-symmetrical (N-
methyl)benzylamino substituent) recorded in CDCl3 solution at
25◦C showed two separate sets of resonances for the benzylic
methylene group and for the N-methyl moiety. This ‘twin reso-
nance’effect was also observed in [D6]DMSO, but the difference
in chemical shifts was much smaller in this solvent. When the
spectrum was recorded in [D6]DMSO at 85◦C, both pairs of
resonances coalesced to single signals. On cooling to 25◦C, the
resonances reverted to twin signals. These observations suggest
that compounds 6 also exist as two rotamers that interconvert by
R3
R3
N
R2
N
R2
N
N
N
N
N
N
R1
R1
N
N
S
S
S
S
O
O
O
O
8
9
Fig. 4. Possible isomers of 6 and 7.
R2
R2
H
H
HCl
N
S
N
S
Nꢀ
N
R1
Clꢁ
R1
7
N
N
N
O
N
N
O
N
S
S
R3
R3
O
Cl
O
Rotation about
S-triazole bond
and tautomerization
R2
N
H
R2
N
S
N
S
R3
N
R1
R1
ꢁHCl
R3
N
N
N
N
N
N
S
S
O
O
O
Cl
O
6
Scheme 4.

336
T. Cablewski, C. L. Francis, and A. J. Liepa
slow rotation of the dialkylamino substituent as noted previously
in related systems.[8–10]
(EI) 282 (100%, M+•), 212 (18), 148 (94). The organic layer
of the mother liquor (from the original precipitation) was dried
and evaporated and the residue was purified by radial chromato-
graphy. Elution with 0–2% methanol in dichloromethane
afforded more of the title compound (11%).
Conclusions
The dichloro compounds 1, readily available 1,3-dielectrophiles,
have been shown to react with two types of 2-mercapto-1H-
azaheterocyclic compounds, as further representatives of readily
available 1,3-dinucleophiles. These condensations provide a
convenient pathway to several new, fused [1,4,2,6]dithiadiazine
ring systems. It is apparent that this methodology could be
extended to include other 2-mercapto-1H-azaheterocycles.
3-Diethylamino-1,1-dioxo-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3b
No precipitate was obtained. The organic layer was dried and
evaporated and the residue was purified by radial chromato-
graphy. Elution with 0–2% methanol in dichloromethane
afforded the title compound (27%) as a white solid, which was
recrystallized by slow evaporation from methanol/chloroform
solution affording colourless prisms, mp 178–179◦C. (Found:
C 46.7, H 4.5, N 18.1; M+• 310.0553. C12H14N4O2S2 requires
C 46.4, H 4.6, N 18.1%; M+• 310.0553). δH (400 MHz) 8.03–
7.97 (1H, m, ArH), 7.75–7.69 (1H, m, ArH), 7.44–7.35 (2H, m,
ArH), 3.78 (2H, q, J 7, NCH2), 3.65 (2H, q, J 7, NCH2), 1.39
(3H, t, J 7, CH3), 1.33 (3H, t, J 7, CH3). δC 159.0, 141.2, 141.1,
131.2, 125.0, 124.7, 119.3, 113.3, 46.7, 45.6, 13.2, 12.4. m/z
(EI) 310 (42%, M+•), 279 (10), 215 (18), 167 (17), 149 (81),
148 (100).
Experimental
Methods and Materials
General experimental conditions, including those for the crys-
tallography, have been described previously.[7,10] Negative-ion
atmospheric pressure chemical ionization (APCI) mass spectra
were acquired with a VG Platform mass spectrometer using a
cone voltage of 50V and with the source maintained at 100◦C.
Nitrogen was used as the nebulizer and sheath gas and the
probe temperature was 400◦C. The solvent used was acetonitrile
with a flow rate of 0.3 mL min−1. Benzylmethylcyanamide,[14]
5,6-dichloro-2-mercaptobenzimidazole 2b,[15,16] and 5-chloro-
2-mercaptobenzimidazole 2d[16] were prepared by literature
procedures. N,N-Dialkyl-Nꢀ-chlorosulfonylchloroformamidines
1a–e were prepared by literature procedures[1,2,6] and used as
crude products. Other materials were obtained from commercial
sources. Reactionswerecarriedoutunderanitrogenatmosphere.
1,1-Dioxo-3-pyrrolidin-1-yl-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3c
Precipitated and then recrystallized from ethyl acetate in 50%
yield; colourless crystals, mp 227.5–228.5◦C (Found: C 46.9,
H 3.9, N 18.3; M+• 308.0393. C12H12N4O2S2 requires C 46.7,
H 3.9, N 18.2%; M+• 308.0396). δH (400 MHz) 8.02–7.96 (1H,
m, ArH), 7.76–7.68 (1H, m, ArH), 7.43–7.35 (2H, m, ArH),
3.83 (2H, t, J 7, NCH2), 3.63 (2H, t, J 7, NCH2), 2.18–2.10 (2H,
m, CH2), 2.10–2.02 (2H, m, CH2). δC 156.9, 141.2, 141.1, 131.1,
124.9, 124.7, 119.3, 113.3, 51.3, 48.9, 25.5, 24.4. m/z (EI) 308
(70%, M+•), 212 (11), 148 (100).
1H-Naphtho[2,3-d]imidazole-2-thiol 2c
Prepared by the procedure of Brown.[17] δH ([D6]DMSO) 12.64
(1H, br, SH), 7.98–7.88 (2H, m, ArH), 7.56 (2H, s, ArH), 7.42–
7.32 (2H, m, ArH). m/z (electron impact [EI]) 200 (100%, M+•).
1,1-Dioxo-3-piperidin-1-yl-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3d
General Synthesis Procedures
3-Dialkylamino-1,1-dioxo-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazoles 3
Precipitated and then recrystallized from ethanol in 52%
yield; colourless prisms, mp 199–200◦C (Found: C 48.5,
H 4.4, N 17.6; M+• 322.0549. C13H14N4O2S2 requires C 48.4,
H 4.4, N 17.4%; M+• 322.0553). δH (400 MHz) 8.01–7.96
(1H, m, ArH), 7.74–7.68 (1H, m, ArH), 7.43–7.34 (2H, m,
ArH), 3.96 (2H, m, NCH2), 3.72 (2H, m, NCH2), 1.75 (6H,
m, CH2CH2CH2). δC 158.3, 141.2, 141.1, 131.3, 125.0, 124.8,
119.3, 113.3, 49.9, 49.4, 26.0, 25.4, 23.7. m/z (EI) 322 (50%,
A mixture of the 2-mercaptobenzimidazole 2 (2 mmol), the
dichloro compound 1 (3 mmol) and N,N-diisopropylethylamine
(8 mmol) in DMPU (2 mL) was stirred at room temperature for
3 to 6 h. Ethyl acetate (8 mL) was stirred in, followed by water
(15 mL).The mixture was acidified to pH 3 by the dropwise addi-
tion of concentrated hydrochloric acid and the resulting mixture
stirred vigorously at room temperature for 1 h. In cases where a
precipitate did not appear quickly, diethyl ether (3 to 5 mL) was
added and the mixture stirred a little longer. The precipitate was
collected by filtration and washed sequentially with water, ethyl
acetate, and diethyl ether to provide the title compounds.
The following compounds were prepared by the above
procedure.
M
+•), 212 (10), 148 (100).
1,1-Dioxo-3-(N-methyl)benzylamino-1λ6-
[1,4,2,6]dithiadiazino[2,3-a]benzimidazole 3e
Precipitated in 27% yield. Recrystallized from ethyl
acetate/petroleum spirit; small white needles, mp 174–175◦C.
(Found: C 53.7, H 4.0, N 15.7; M+ 358.0548. C16H14N4O2S2
requires C 53.6, H 3.9, N 15.6%; M+• 358.0553). δH (500 MHz)
8.02 (1H, t, J 7.3, ArH), 7.74 (1H, t, J 7.3, ArH), 7.46–7.30
(6H, m, ArH), 7.28–7.24 (1H, m, ArH), 5.00 and 4.83 (2H,
2s, NCH2), 3.37 and 3.24 (3H, 2s, NCH3). δH (500 MHz,
[D6]DMSO, 30◦C) 7.90–7.86 (1H, m, ArH), 7.81–7.75 (1H, m,
ArH), 7.50–7.33 (7H, m, ArH), 5.04 and 5.02 (2H, 2 s,
NCH2), 3.37 and 3.35 (3H, 2 s, NCH3). δH (500 MHz,
[D6]DMSO, 100◦C) 7.90–7.86 (1H, m, ArH), 7.76 (1H, d, J
7.4, ArH), 7.50–7.34 (7H, m, ArH), 5.03 (2H, s, NCH2), 3.37
(3H, s, NCH3). δC 160.4, 159.5, 142.0, 141.9, 140.92, 140.88,
3-Dimethylamino-1,1-dioxo-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3a
Precipitated in 68% yield. An analytical sample was recrys-
tallized from ethyl acetate; colourless crystals, mp 201–202◦C.
(Found: C 42.7, H 3.5, N 20.0; M+• 282.0238. C10H10N4O2S2
requires C 42.5, H 3.6, N 19.8%; M+• 282.0240). δH (200 MHz)
8.06–7.95 (1H, m, ArH), 7.80–7.67 (1H, m, ArH), 7.48–7.34
(2H, m,ArH), 3.41 (3H, s, NCH3), 3.37 (3H, s, NCH3). δC 160.2,
141.1, 141.0, 131.0, 125.1, 124.9, 119.3, 113.3, 41.0, 39.4. m/z

Preparation of Some Fused [1,4,2,6]Dithiadiazine Dioxides
337
Table 3. Crystal data and structure refinement for 3c, 3g, 3k, and 3m
Parameter
3c
3g
3k
3m
CCDC deposition no.
Empirical formula
Formula weight
Temperature [K]
Wavelength [Å]
Crystal system
Space group
Unit cell dimensions
a [Å]
677996
C12H12N4O2S2
308.38
677997
C12H12Cl2N4O2S2
379.28
677998
C10H9ClN4O2S2
316.78
677999
C13H16N4O3S2
340.42
123(2)
123(2)
123(2)
123(2)
0.71073
Monoclinic
P21/c
0.71073
Triclinic
P¯ı
0.71073
Triclinic
P¯ı
0.71073
Triclinic
P¯ı
7.9493(1)
9.0304(1)
17.5643(3)
90
92.3787(6)
90
1259.77(3)
4
1.626
8.5356(1)
9.2656(1)
10.2599(2)
107.1449(12)
98.1531(8)
91.2385(7)
765.806(19)
2
1.645
0.707
0.21 × 0.20 × 0.12
3.67 to 28.17
12950
9.1802(1)
9.6033(1)
15.6647(3)
96.7124(6)
90.3552(6)
116.0126(10)
1230.04(3)
4
1.711
0.652
0.21 × 0.20 × 0.17
3.72 to 28.16
19697
7.6261(1)
9.7994(1)
11.1762(2)
65.924(1)
79.417(1)
77.270(2)
739.674(18)
2
1.528
0.378
0.42 × 0.35 × 0.18
3.58 to 28.19
12274
b [Å]
c [Å]
α [◦]
β [◦]
γ [◦]
Volume [Å3]
Z
Density (calc.) [Mg m−3
]
Absorption coeff. [mm−1
Crystal size [mm3]
θ range [◦]
]
0.430
0.25 × 0.22 × 0.14
2.56 to 28.30
15009
3053
0.0339
Reflections collected
Independent reflections
R(int)
3689
0.0350
5900
0.0368
3550
0.0196
No. reflections included in refinement
3053
3689
5900
3550
Observed reflections [I > 2σ(I)]
2578
3065
5036
3258
Final R indices [I > 2σ(I)]
R1
wR2
0.0329
0.0730
0.0325
0.0795
0.0330
0.0825
0.0296
0.0726
R indices (all data)
R1
wR2
0.0438
0.0779
1.044
0.0445
0.0861
1.045
0.0420
0.0870
1.021
0.0334
0.0745
1.028
Goodness-of-fit on F2
134.3, 133.8, 130.4, 130.3, 129.1, 128.8, 128.3, 128.1, 127.9,
127.3, 125.0, 124.9, 119.3, 112.6, 112.5, 55.6, 55.5, 37.7. m/z
(EI) 358 (100%, M+•), 239 (35), 148 (90).
mother liquor (from the original precipitation) was dried and
evaporated and the residue was purified by radial chromato-
graphy. Elution with dichloromethane afforded more of the title
compound (20%).
7,8-Dichloro-3-dimethylamino-1,1-dioxo-1λ6-
[1,4,2,6]dithiadiazino[2,3-a]benzimidazole 3f
3-Diethylamino-1,1-dioxo-1λ6-[1,4,2,6]dithiadiazino
[2,3-a]benz[f]benzimidazole 3h
Precipitated in 76% yield. Recrystallized from chloroform/
methanol (∼1:2); pale fawn rhombs, mp 255–257◦C (dec.).
(Found: C 34.3, H 2.3, N 16.0; M+• 349.9464. C10H8Cl2N4O2S2
requires C 34.2, H 2.3, N 16.0%; M+• 349.9460). δH
(500 MHz) 8.13 (1H, s, ArH), 7.96 (1H, s, ArH), 3.39 (3H,
s, NCH3), 3.33 (3H, s, NCH3). δC ([D6]DMSO) 169.0,
144.9, 140.4, 129.6, 127.7, 127.5, 120.8, 113.6, 41.0. m/z
(EI) 354/352/350 (16/65/89%, M+•), 284/282/280 (4/16/21),
220/218/216 (12/58/87), 181 (100).
Precipitatedin37%yield. Recrystallizedfromethanol;small,
white needles, mp 222–223◦C. (Found: C 53.1, H 4.5, N 15.4;
M
+• 360.0701. C16H16N4O2S2 requires C 53.3, H 4.5, N 15.5%;
M+• 360.0709). δH (400 MHz) 8.45 (1H, s, ArH), 8.19 (1H,
s, ArH), 8.05–7.97 (2H, m, ArH), 7.54–7.47 (2H, m, ArH),
3.83 (2H, q, J 7, NCH2), 3.69 (2H, q, J 7, NCH2), 1.43 (3H,
t, J 7, CH3), 1.37 (3H, t, J 7, CH3). δC 158.2, 145.3, 140.6,
131.24, 131.22, 130.4, 128.4, 128.2, 125.6, 125.1, 116.6, 110.2,
46.7, 45.6, 13.2, 12.4. m/z (EI) 360 (100%, M+•), 262 (14), 198
(95), 140 (94). The organic layer of the mother liquor (from
the original precipitation) was dried and evaporated and the
residue was purified by radial chromatography. Elution with
dichloromethane afforded more of the title compound (6%).
7,8-Dichloro-3-diethylamino-1,1-dioxo-1λ6-
[1,4,2,6]dithiadiazino[2,3-a]benzimidazole 3g
Precipitated in 39% yield. Recrystallized from ethyl
acetate/petroleum spirit (∼1:1); colourless rhombs, mp 211–
212◦C. (Found: C 38.1, H 3.2, N 14.6; M+• 377.9761.
C12H12Cl2N4O2S2 requires C 38.0, H 3.2, N 14.8%; M+•
377.9773). δH (400 MHz) 8.12 (1H, s, ArH), 7.82 (1H, s, ArH),
3.80 (2H, q, J 7, NCH2), 3.67 (2H, q, J 7, NCH2), 1.42
(3H, t, J 7, CH3), 1.35 (3H, t, J 7, CH3). δC 158.8, 143.2,
140.5, 130.2, 129.3, 129.2, 120.5, 114.7, 47.0, 45.8, 13.1, 12.4.
m/z (EI) 382/380/378 (8/32/46%, M+•), 284/282/280 (2/8/11),
220/218/216 (12/65/100), 181 (88). The organic layer of the
1,1-Dioxo-3-piperidin-1-yl-1λ6-[1,4,2,6]dithiadiazino
[2,3-a]benz[f]benzimidazole 3i
Precipitated in 76% yield. Recrystallized from chloroform/
methanol (∼1:2); off-white crystals, mp 248–250◦C (dec.).
(Found: C 54.6, H 4.4, N 14.8; M+• 372.0714. C17H16N4O2S2
requires C 54.8, H 4.3, N 15.0%; M+• 372.0709). δH (400 MHz)
8.43 (1H, s, ArH), 8.18 (1H, s, ArH), 8.04–7.97 (2H, m, ArH),

338
T. Cablewski, C. L. Francis, and A. J. Liepa
7.54–7.46 (2H, m, ArH), 4.00 (2H, m, NCH2), 3.75 (2H, m,
NCH2), 1.79 (6H, m, CH2CH2CH2). δC 157.5, 145.3, 140.2,
131.27, 131.24, 130.3, 128.4, 128.2, 125.7, 125.2, 116.5, 110.3,
49.9, 49.4, 26.0, 25.3, 23.7. m/z (EI) 372 (100%, M+•), 262 (8),
198 (72), 140 (75).
1,1-Dioxo-7-methoxy-3-piperidin-1-yl-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3n and
1,1-Dioxo-8-methoxy-3-piperidin-1-yl-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3o
The precipitate (a mixture of 3n and 3o, 36% yield) was puri-
fied by radial chromatography. The organic layer of the mother
liquor (from the original precipitation) was dried and evapo-
rated and the residue was also purified by radial chromatography.
In each procedure, the mobile phase used was 33–50% ethyl
acetate in petroleum spirit. Combination of appropriate frac-
tions from both procedures afforded the following. (i) The title
compound 3n (11%), recrystallized from ethanol; white nee-
dles, mp 185–186◦C. (Found: C 47.9, H 4.6, N 16.2; M+•
352.0651. C14H16N4O3S2 requires C 47.7, H 4.6, N 15.9%;
M+• 352.0658). δH (400 MHz) 7.60 (1H, d, J 9, ArH), 7.47
(1H, d, J 2.5, ArH), 7.01 (1H, dd, J 9, 2.5, ArH), 3.99 (2H,
m, NCH2), 3.90 (3H, s, OMe), 3.75 (2H, m, NCH2), 1.79 (6H,
m, CH2CH2CH2). δC 158.6, 158.0, 138.7, 135.4, 132.2, 119.7,
114.8, 96.3, 56.0, 49.9, 49.5, 26.0, 25.4, 23.8. m/z (EI) 352 (75%,
7-Chloro-3-dimethylamino-1,1-dioxo-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3j and
8-Chloro-3-dimethylamino-1,1-dioxo-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3k
The precipitate (a mixture of 3j and 3k, 46% yield) was puri-
fied by radial chromatography. The organic layer of the mother
liquor (from the original precipitation) was dried and evapo-
rated and the residue was also purified by radial chromatography.
In each procedure, the mobile phase used was 50–100% ethyl
acetate in petroleum spirit and then 0–20% ethyl acetate in
dichloromethane. Combination of appropriate fractions from
both procedures afforded the following compounds. (i) The
title compound 3j (19%), recrystallized from methanol; white
needles, mp 229–230◦C. (Found: C 38.1, H 2.9, N 17.6; M+•
315.9809. C10H9ClN4O2S2 requires C 37.9, H 2.9, N 17.7%;
M+• 315.9850). δH (400 MHz) 7.92 (1H, d, J 8.8, ArH), 7.72
(1H, d, J 1.9, ArH), 7.39 (1H, dd, J 8.8, 1.9, ArH), 3.42 (3H,
s, NCH3), 3.38 (3H, s, NCH3). δC 160.2, 142.4, 142.1, 130.6,
129.7, 125.5, 119.3, 114.1, 41.1, 39.5. m/z(EI)318/316(22/53%,
M
+•), 242 (8), 178 (100). (ii) A mixture of 3n and 3o (38%).
(iii) The title compound 3o (13%), recrystallized from ethanol;
colourless needles, mp 184.5–185◦C. (Found: C 47.6, H 4.5,
N 16.0; M+• 352.0655. C14H16N4O3S2 requires C 47.7, H 4.6,
N 15.9%; M+• 352.0658). δH (400 MHz) 7.87 (1H, d, J 9, ArH),
7.19 (1H, d, J 2.5, ArH), 7.04 (1H, dd, J 9, 2.5, ArH), 3.98 (2H,
m, NCH2), 3.87 (3H, s, OMe), 3.74 (2H, m, NCH2), 1.79 (6H,
m, CH2CH2CH2). δC 158.3, 157.8, 142.0, 141.0, 125.7, 114.6,
113.7, 101.6, 55.8, 49.9, 49.5, 26.0, 25.4, 23.8. m/z (EI) 340
(80%, M+•), 242 (7), 178 (100).
M
+•), 184/182 (16/40), 149 (100). (ii) A mixture of 3j and 3k
(16%). (iii) The title compound 3k (18%), recrystallized from
methanol; white needles, mp 237–238◦C. (Found: C 37.9, H
2.9, N 17.7; M+• 315.9813. C10H9ClN4O2S2 requires C 37.9,
H 2.9, N 17.7%; M+• 315.9850). δH (400 MHz) 8.03 (1H, d,
J 1.8, ArH), 7.64 (1H, d, J 8.4, ArH), 7.37 (1H, dd, J 8.4, 1.8,
ArH), 3.42 (3H, s, NCH3), 3.38 (3H, s, NCH3). δC ([D6]DMSO)
159.1, 143.2, 139.8, 130.9, 129.3, 125.3, 120.8, 112.2, 40.9, 39.8.
m/z (EI) 318/316 (42/100%, M+•), 248/246 (10/24), 184/182
(26/67), 147 (45). (iv)The starting 2-mercaptobenzimidazole 2d
(11%).
5-Substituted-3-mercapto[1,2,4]triazoles 5b–f
5-Isopropyl-3-mercapto[1,2,4]triazole 5b,[18] 5-tert-butyl-3-
mercapto[1,2,4]triazole 5c,[19] 3-mercapto-5-phenyl[1,2,4]
triazole 5d,[20,21] 5-(4-tert-butylphenyl)-3-mercapto[1,2,4]
triazole 5e,[22] and 3-mercapto-5-(4-pyridyl)[1,2,4]triazole
5f[21] werepreparedbymodificationofaliteratureprocedure.[21]
Thus, a mixture of the appropriate hydrazide (30 mmol) and
ammonium thiocyanate (45 mmol) in a conical flask was melted
at 170–180◦C on a hotplate. Heating was continued until bub-
bling ceased and the mixture began to solidify (60–90 min). The
mixture was removed from the hotplate and allowed to cool
slightly. Water (15–20 mL) was added slowly with stirring and
the mixture briefly brought to the boil.The mixture was cooled to
room temperature then cooled further in ice and filtered.The col-
lected solid was dissolved in aqueous sodium carbonate solution
(10%) with stirring and gentle heating. Any insoluble material
was filtered off and the filtrate slowly acidified with concen-
trated hydrochloric acid. The precipitated solid was collected
by filtration, washed on the filter with water and then dried to
provide the title compounds, which were used without further
purification.
3-Diethylamino-1,1-dioxo-7-methoxy-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3l and
3-Diethylamino-1,1-dioxo-8-methoxy-1λ6-[1,4,2,6]
dithiadiazino[2,3-a]benzimidazole 3m
No precipitate formed. The organic layer was dried and evap-
orated and the residue was purified by radial chromatography.
Elution with 33–50% ethyl acetate in petroleum spirit afforded
three fractions. (i) The title compound 3l (11%), recrystallized
from ethanol; small, white crystals, mp 145.5–146◦C. (Found:
C 45.9, H 4.8, N 16.4; M+• 340.0660. C13H16N4O3S2 requires
C 45.9, H 4.7, N 16.5%; M+• 340.0658). δH (400 MHz) 7.60
(1H, d, J 9, ArH), 7.47 (1H, d, J 2.5, ArH), 7.00 (1H, dd, J 9,
2.5, ArH), 3.90 (3H, s, OMe), 3.80 (2H, q, J 7, NCH2), 3.66
(2H, q, J 7, NCH2), 1.41 (3H, t, J 7, CH3), 1.34 (3H, t, J 7,
CH3). δC 159.3, 158.0, 138.7, 135.4, 132.1, 119.7, 114.8, 96.3,
56.0, 46.7, 45.7, 13.2, 12.4. m/z (EI) 340 (72%, M+•), 242 (11),
178 (100). (ii) A mixture of 3l and 3m (5%). (iii) The title
compound 3m (13%), recrystallized from ethanol; colourless
prisms, mp 174.5–175.5◦C. (Found: C 45.9, H 4.7, N 16.4;
5b: δH ([D6]DMSO) 13.14 (1H, br s, NH/SH), 13.07 (1H, br
s, SH/NH), 2.83 (1H, sep, J 7, CH), 1.16 (6H, d, J 7, CMe2). δC
([D6]DMSO) 166.6, 157.5, 26.1, 20.5. m/z (APCI) 142 (100%,
M − H•).
5c: δH ([D6]DMSO) 13.14 (2H, br s, NH + SH), 1.21 (9H, s,
C(CH3)3). δC ([D6]DMSO) 166.8, 159.9, 31.8, 28.3. m/z (APCI)
156 (100%, M − H•), 124 (43, M − SH•).
M
M
+• 340.0666. C13H16N4O3S2 requires C 45.9, H 4.7, N 16.5%;
+• 340.0658). δH (400 MHz) 7.88 (1H, d, J 9, ArH), 7.19 (1H,
d, J 2.5, ArH), 7.04 (1H, dd, J 9, 2.5, ArH), 3.87 (3H, s, OMe),
3.80 (2H, q, J 7, NCH2), 3.66 (2H, q, J 7, NCH2), 1.41 (3H, t,
J 7, CH3), 1.34 (3H, t, J 7, CH3). δC 158.9, 157.8, 142.0, 141.0,
125.7, 114.6, 113.7, 101.6, 55.8, 46.7, 45.6, 13.2, 12.4. m/z (EI)
340 (92%, M+•), 242 (10), 178 (100).
5d: δH ([D6]DMSO) 13.82 (1H, br s, NH/SH), 13.66 (1H, br
s, SH/NH), 7.92–7.86 (2H, m, ArH), 7.52–7.46 (3H, m, ArH).
δC ([D6]DMSO) 167.5, 150.6, 131.0, 129.5, 126.1, 125.9.
5e: δH ([D6]DMSO) 13.76 (1H, br s, NH/SH), 13.60 (1H, br
s, SH/NH), 7.82 (2H, d, J 8.4,ArH), 7.50 (2H, d, J 8.9,ArH), 1.27

Preparation of Some Fused [1,4,2,6]Dithiadiazine Dioxides
339
(9H, s, C(CH3)3). δC ([D6]DMSO) 167.3, 153.8, 150.6, 126.3,
125.9, 123.2, 35.1, 31.3.
5f : δH ([D6]DMSO) 13.91 (2H, br, NH + SH), 8.73–8.69
(2H, m, ArH), 7.84–7.80 (2H, m, ArH). δC ([D6]DMSO) 168.1,
151.1, 148.8, 132.9, 119.9. m/z (APCI) 177 (100%, M − H•),
145 (81, M − SH•).
Mp 62–66◦C. We were unable to find suitable recrystallization
conditions. (Found M+• 303.0803. C10H17N5O2S2 requires M+•
303.0818). (Found: C 37.4, H 6.1, N 21.3; C10H17N5O2S2 H2O
requires C 37.4, H 6.0, N 21.8%). δH 3.76 (2H, q, J 7, CH2),
3.64 (2H, q, J 7, CH2), 3.61 (1H, sep, J 7, CH), 1.45 (6H, d,
J 7, CMe2), 1.37 (3H, t, J 7, CH3), 1.30 (3H, t, J 7, CH3). δC
159.5, 159.0, 142.0, 47.3, 46.1, 27.0, 20.9, 13.0, 12.4. m/z (EI)
303 (61%, M+•), 288 (17), 143 (70), 98 (88), 84 (96), 55 (100).
3-Dialkylamino-1,1-dioxo-1λ6-[1,2,4]triazolo[2,3-b]
[1,4,2,6]dithiadiazines 6 and
6-tert-Butyl-1,1-dioxo-3-pyrrolidino-1λ6-[1,2,4]triazolo
[2,3-b][1,4,2,6]dithiadiazine 6c
3-Dialkylamino-1,1-dioxo-1λ6-[1,2,4]triazolo[4,3-b]
[1,4,2,6]dithiadiazines 7
Precipitated in 63% yield. An analytical sample was obtained by
radial chromatography, with dichloromethane as eluent; whi+te•
solid, mp 210–211◦C. (Found: C 41.8, H 5.5, N 22.1; M
315.0819. C11H17N5O2S2 requires C 41.9, H 5.4, N 22.2%; M+•
315.0818). δH 3.80 (2H, t, J 7, NCH2), 3.59 (2H, t, J 7, NCH2),
2.17 (2H, m, CH2), 2.07 (2H, m, CH2), 1.36 (9H, s, CMe3). δC
172.3, 154.6, 144.6, 51.7, 49.0, 33.4, 29.0, 25.6, 24.5. m/z (EI)
315 (34%, M+•), 300 (82), 191 (100).
A mixture of the 3-mercapto[1,2,4]triazole 5 (2 mmol), the
dichlorocompound 1(2.6 mmol)andN,N-diisopropylethylamine
(8 mmol) in DMPU (3 mL) was stirred at room temperature for
4 h. Ethyl acetate (10 mL) was stirred in, followed by water
(20 mL) and the resulting mixture stirred vigorously at room
temperature for 1 h. Any precipitate was collected by filtra-
tion and washed sequentially with water, ethyl acetate, and
diethyl ether, then purified by radial chromatography and/or
recrystallization to provide the title compounds. Where no pre-
cipitatewasobtained, theorganicphasewasdriedandevaporated
under reduced pressure. The residue was purified by radial
chromatography on silica gel to provide the title compounds.
The following compounds were prepared by the above
procedure.
3-Diethylamino-1,1-dioxo-6-phenyl-1λ6-[1,2,4]triazolo
[2,3-b][1,4,2,6]dithiadiazine 6d
The residue from evaporation of the organic phase was recrystal-
lized from dichloromethane/methanol to give the title compound
(15%) as large, colourless needles, mp 187–188◦C. (Found: C
46.4, H 4.5, N 20.8; M+• 337.0655. C13H15N5O2S2 requires C
46.3, H 4.5, N 20.8%; M+• 337.0662). δH 8.18–8.13 (2H, m,
ArH), 7.48–7.43 (3H, m, ArH), 3.78 (2H, q, J 7, CH2), 3.63 (2H,
q, J 7, CH2), 1.40 (3H, t, J 7, CH3), 1.34 (3H, t, J 7, CH3). δC
162.4, 156.5, 145.4, 130.6, 128.8, 128.7, 127.1, 47.2, 46.0, 13.0,
12.4. m/z (EI) 337 (62%, M+•), 147 (87), 103 (100).
1,1-Dioxo-3-piperidino-1λ6-[1,2,4]triazolo[2,3-b][1,4,2,6]
dithiadiazine 6a and
1,1-Dioxo-3-piperidino-1λ6-[1,2,4]triazolo[4,3-b]
[1,4,2,6]dithiadiazine 7a
Elution with 50–100% dichloromethane in petroleum spirit
afforded 6a in 30% yield. Recrystallized by slow evaporation
from chloroform; colourless rhombs, mp 155–156◦C. (Found:
C 35.3, H 4.0, N 25.5; M+• 273.0346. C8H11N5O2S2 requires
C 35.2, H 4.1, N 25.6%; M+• 273.0349). δH 8.14 (1H, s,
ArH), 3.97 (2H, m, NCH2), 3.70 (2H, m, NCH2), 1.78 (6H, m,
CH2CH2CH2). δC 156.0, 151.5, 145.1, 50.3, 50.0, 26.0, 25.3,
23.6. m/z (EI) 273 (58%, M+•), 111 (64), 109 (58), 71 (100).
Further elution with 0–10% ethyl acetate in dichloromethane
gave 7a in 21% yield. Recrystallized from benzene; colourle+ss•
prisms, mp 120–121◦C. (Found: C 35.4, H 4.1, N 25.5; M
273.0344. C8H11N5O2S2 requires C 35.2, H 4.1, N 25.6%; M+•
273.0349). δH 8.76 (1H, s, ArH), 3.98 (2H, m, NCH2), 3.77 (2H,
m, NCH2), 1.79 (6H, m, CH2CH2CH2). δC 158.7, 142.5, 138.9,
50.62, 50.58, 26.0, 25.4, 23.6. m/z (EI) 273 (88%, M+•), 111
(71), 109 (72), 71 (100).
1,1-Dioxo-6-phenyl-3-piperidino-1λ6-[1,2,4]triazolo
[2,3-b][1,4,2,6]dithiadiazine 6e
The precipitate was taken up in dichloromethane and filtered
through a short column of silica gel to afford the title compound
(49%) as a white solid, mp 240–241◦C. (Found: C 48.1, H 4.4,
N 19.9; M+• 349.0655. C14H15N5O2S2 requires C 48.1, H 4.3,
N 20.0%; M+• 349.0662). δH 8.19–8.13 (2H, m, ArH), 7.48–
7.44 (3H, m, ArH), 4.02–3.97 (2H, m, NCH2), 3.74–3.68 (2H,
m, NCH2), 1.85–1.75 (6H, m, CH2CH2CH2). δC 162.5, 155.9,
145.4, 130.6, 128.8, 128.7, 127.1, 50.2, 49.8, 26.0, 25.4, 23.7.
m/z (EI) 349 (50%, M+•), 177 (100).
6-(4-tert-Butylphenyl)-3-dimethylamino-1,1-dioxo-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6f
Elution with 0–5% ethyl acetate in dichloromethane afforded 6f
in 53% yield. Recrystallized from methanol; small, colourless
crystals, mp 225–226◦C. (Found: C 49.4, H 5.1, N 19.3; M+•
365.0967. C15H19N5O2S2 requires C 49.3, H 5.2, N 19.2%; M+•
365.0961). δH 8.08 (2H, m, ArH), 7.47 (2H, m, ArH), 3.41 (3H,
s, CH3), 3.36 (3H, s, CH3), 1.35 (9H, s, CMe3). δC 162.6, 157.8,
154.0, 145.1, 126.8, 125.9, 125.7, 41.3, 39.6, 34.9, 31.2. m/z (EI)
365 (34%, M+•), 350 (100).
3-Diethylamino-1,1-dioxo-6-isopropyl-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6b and
3-Diethylamino-1,1-dioxo-7-isopropyl-1λ6-
[1,2,4]triazolo[4,3-b][1,4,2,6]dithiadiazine 7b
Elution with 50–100% dichloromethane in petroleum spirit
afforded 6b in 15% yield. Recrystallized from methanol; colour-
less crystals, mp 107–108◦C. (Found: C 39.6, H 5.8, N 22.8;
M
+• 303.0817. C10H17N5O2S2 requires C 39.6, H 5.7, N 23.1%;
6-(4-tert-Butylphenyl)-3-diethylamino-1,1-dioxo-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6g and
7-(4-tert-Butylphenyl)-3-diethylamino-1,1-dioxo-1λ6-
[1,2,4]triazolo[4,3-b][1,4,2,6]dithiadiazine 7g
M+• 303.0818). δH 3.76 (2H, q, J 7, CH2), 3.60 (2H, q, J 7,
CH2), 3.14 (1H, sep, J 7, CH), 1.38 (3H, t, J 7, CH3), 1.34
(6H, d, J 7, CMe2), 1.31 (3H, t, J 7, CH3). δC 169.9, 156.5,
144.8, 47.1, 45.9, 28.4, 21.1, 13.0, 12.3. m/z (EI) 303 (12%,
M
+•), 193 (100). Further elution with 0–10% ethyl acetate in
Elution with dichloromethane afforded 6g in 29% yield.
dichloromethane gave 7b as a white waxy solid in 23% yield.
Recrystallized from isopropanol; white needles, mp 141–142◦C.

340
T. Cablewski, C. L. Francis, and A. J. Liepa
Table 4. Crystal data and structure refinement for 6a, 7a, 6d, and 6j
Parameter
6a
7a
6d
6j
CCDC deposition no.
Empirical formula
Formula weight
Temperature [K]
Wavelength [Å]
Crystal system
Space group
Unit cell dimensions
a [Å]
678000
C8H11N5O2S2
273.34
678001
C8H11N5O2S2
273.34
678002
C13H15N5O2S2
337.42
678003
C10H10N6O2S2
310.36
123(2)
0.71073
123(2)
123(2)
123(2)
0.71073
Triclinic
P¯ı
0.71073
Monoclinic
P21/c
0.71073
Monoclinic
P21/n
Orthorhombic
Pnma
7.6560(2)
9.0486(2)
9.1919(2)
69.911(1)
73.195(1)
89.213(1)
569.90(2)
2
1.593
0.465
0.30 × 0.30 × 0.18
2.41 to 27.50
7385
13.0142(2)
8.6239(2)
20.5607(4)
90
101.453(3)
90
2261.64(8)
8
1.606
7.1761(4)
13.5404(7)
15.2641(10)
90
92.265(4)
90
1482.01(15)
4
1.512
13.4347(7)
6.5913(4)
14.4292(8)
90
90
90
1277.74(12)
4
1.613
b [Å]
c [Å]
α [◦]
β [◦]
γ [◦]
Volume [Å3]
Z
Density (calc.) [Mg m−3
]
]
Absorption coeff. [mm−1
Crystal size [mm3]
θ range [◦]
0.469
0.374
0.428
0.30 × 0.25 × 0.20
2.02 to 27.50
20354
5161
0.0657
0.50 × 0.35 × 0.33
2.67 to 30.46
60130
6818
0.0240
0.60 × 0.55 × 0.35
2.82 to 30.10
19477
2032
0.0265
2032
Reflections collected
Independent reflections
R(int)
2503
0.0597
2503
No. reflections included in refinement
5161
6818
Observed reflections [I > 2σ(I)]
2271
3502
6337
1901
Final R indices [I > 2σ(I)]
R1
wR2
0.0299
0.0785
0.0460
0.0927
0.0346
0.1081
0.0296
0.0806
R indices (all data)
R1
wR2
0.0340
0.0806
1.066
0.0884
0.1098
1.026
0.0380
0.1111
1.077
0.0323
0.0830
1.072
Goodness-of-fit on F2
(Found: C 51.9, H 5.8, N 17.8; M+• 393.1287. C17H23N5O2S2
requires C 51.9, H 5.9, N 17.8%; M+• 393.1288). δH 8.08 (2H,
m, ArH), 7.47 (2H, m, ArH), 3.79 (2H, q, J 7, CH2), 3.64 (2H, q,
J 7, CH2), 1.42 (3H, t, J 7, CH3), 1.35 (9H, s, CMe3), 1.35 (3H,
t, J 7, CH3). δC 162.5, 156.5, 154.0, 145.2, 126.9, 126.0, 125.7,
47.2, 46.0, 34.9, 31.2, 13.0, 12.4. m/z (EI) 393 (63%, M+•), 378
(100). Further elution gave 7g in 10% yield. Recrystallized from
isopropanol; colourless solid, mp 122–123◦C. (Found: C 52.1,
H 5.7, N 17.7%; M+• 393.1284. C17H23N5O2S2 requires C 51.9,
H 5.9, N 17.8%; M+• 393.1288). δH 7.87 (2H, m, ArH), 7.52
(2H, m, ArH), 3.78 (2H, q, J 7, CH2), 3.67 (2H, q, J 7, CH2),
1.41 (3H, t, J 7, CH3), 1.36 (9H, s, CMe3), 1.32 (3H, t, J 7, CH3).
6-(4-tert-Butylphenyl)-1,1-dioxo-3-piperidino-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6i
Precipitated in 47% yield. Recrystallized from dichloro-
methane/methanol; small, white needles, mp 212–214◦C.
(Found: C 52.9, H 5.8, N 17.2; M+• 405.1287. C18H23N5O2S2
requires C 53.3, H 5.7, N 17.3%; M+• 405.1288). δH 8.08 (2H,
m, ArH), 7.47 (2H, m, ArH), 3.98 (2H, m, NCH2), 3.70 (2H, m,
J 7, NCH2), 1.78 (6H, m, CH2CH2CH2), 1.35 (9H, s, CMe3). δC
162.5, 155.9, 153.9, 145.3, 126.8, 125.9, 125.6, 50.2, 49.8, 34.9,
31.2, 26.0, 25.3, 23.6. m/z (EI) 405 (36%, M+•), 390 (100).
3-Dimethylamino-1,1-dioxo-6-(4-pyridyl)-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6j
δ
C
162.5, 156.5, 153.9, 145.2, 126.8, 125.9, 125.6, 47.1, 45.9,
34.9, 31.2, 13.0, 12.4. m/z (EI) 393 (58%, M+•), 378 (100).
Precipitated in 65% yield. Recrystallized from methanol/
dichloromethane; colourless rhombs, mp 230–231◦C. (Found:
C 38.8, H 3.3, N 27.0; M+• 310.0297. C10H10N6O2S2 requires
C 38.7, H 3.3, N 27.1%; M+• 310.0301). δH 8.75 (2H, m, ArH),
8.07 (2H, m, ArH), 3.45 (3H, s, CH3), 3.39 (3H, s, CH3). δC
160.2, 157.7, 149.7, 146.0, 137.0, 121.2, 41.6, 39.8. m/z (EI)
310 (100%, M+•).
6-(4-tert-Butylphenyl)-1,1-dioxo-3-pyrrolidino-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6h
Elution with 0–5% ethyl acetate in dichloromethane afforded
6h in 43% yield. Recrystallized from isopropanol; colourle+ss•
needles, mp 216–217◦C. (Found: C 52.2, H 5.5, N 18.0; M
391.1141. C17H21N5O2S2 requires C 52.2, H 5.4, N 17.9%; M+•
391.1131). δH 8.07 (2H, m, ArH), 7.47 (2H, m, ArH), 3.84 (2H,
t, J 7, NCH2), 3.62 (2H, t, J 7, NCH2), 2.19 (2H, m, CH2), 2.08
(2H, m, CH2), 1.35 (9H, s, CMe3). δC 162.3, 154.5, 153.9, 145.3,
126.8, 125.9, 125.6, 51.7, 49.0, 34.9, 31.2, 25.6, 24.5. m/z (EI)
391 (52%, M+•), 376 (100).
3-Diethylamino-1,1-dioxo-6-(4-pyridyl)-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6k
Precipitated in 35% yield. Recrystallized from methanol/
dichloromethane (1:1); colourless rhombs, mp 209–210◦C.
(Found: C 42.8, H 4.2, N 24.8; M+• 338.0608. C12H14N6O2S2

Preparation of Some Fused [1,4,2,6]Dithiadiazine Dioxides
341
requires C 42.6, H 4.2, N 24.8%; M+• 338.0614). δH 8.74 (2H,
m, ArH), 8.03 (2H, m, ArH), 3.81 (2H, q, J 7, CH2), 3.66 (2H,
q, J 7, CH2), 1.43 (3H, t, J 7, CH3), 1.35 (3H, t, J 7, CH3).
δC 160.2, 156.5, 150.1, 146.1, 136.6, 121.0, 47.4, 46.2, 13.0,
12.4. m/z (EI) 338 (100%, M+•).
Braybrook for assistance with mass spectrometry, Gary Fallon, Paul Jensen,
and Craig Forsyth (Monash University) for X-ray crystallography, and
E. I. DuPont de Nemours and Co., Agricultural Products Department, for
the biological screening of these compounds.
References
1,1-Dioxo-6-(4-pyridyl)-3-pyrrolidino-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6l
[1] N. Schindler, Chem. Ber. 1973, 106, 56. doi:10.1002/CBER.
19731060109
[2] L. N. Markovskii, Y. G. Shermolovich, V. I. Shevchenko, J. Org.,
U. S. S. R. Chem. (Engl. Transl.) 1973, 9, 644.
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[7] G. D. Fallon, C. L. Francis, K. Johansson, A. J. Liepa,
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CH05070
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Precipitated in 54% yield. Recrystallized from methanol/
dichloromethane; colourless prisms, mp 218–219◦C. (Found: C
43.1, H 3.6, N 25.1; M+• 336.0459. C12H12N6O2S2 requires C
42.9, H 3.6, N 25.0%; M+• 336.0458). δH ([D6]DMSO) 8.76
(2H, m, ArH), 7.97 (2H, m, ArH), 3.72 (4H, m, CH2NCH2),
2.06 (2H, m, CH2), 1.98 (2H, m, CH2). δC ([D6]DMSO) 159.7,
154.3, 150.9, 147.8, 136.3, 121.0, 52.5, 50.2, 25.5, 24.6. m/z (EI)
336 (100%, M+•).
1,1-Dioxo-3-(N-methyl)benzylamino-6-(4-pyridyl)-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6m
Elution with dichloromethane afforded 6m (35%) as a colour-
less solid, mp 170–171◦C. (Found: C 49.7, H 3.8, N 21.5; M+•
386.0602. C16H14N6O2S2 requires C 49.7, H 3.7, N 21.8%;
M
+• 386.0614). δH 8.79–8.71 (2H, m, ArH), 8.07–8.01 (2H, m,
ArH), 7.48–7.24 (5H, m, ArH), 5.01 and 4.83 (2H, 2 s, CH2),
3.39 and 3.27 (3H, 2 s, CH3). δH ([D6]DMSO, 25◦C) 8.81–8.77
(2H, m,ArH), 8.03–7.99 (2H, m,ArH), 7.47–7.34 (5H, m,ArH),
5.04 and 5.03 (2H, 2 s, CH2), 3.39 and 3.35 (3H, 2 s, CH3).
δH ([D6]DMSO, 85◦C) 8.80–8.76 (2H, m, ArH), 8.00–7.96
(2H, m, ArH), 7.48–7.35 (5H, m, ArH), 5.03 (2H, s, CH2),
3.39 (3H, s, CH3). δC 160.3, 160.2, 158.5, 157.6, 149.8, 146.0,
136.82, 136.75, 132.8, 131.8, 129.7, 129.4, 129.2, 128.6, 127.1,
121.1, 56.9, 56.6, 39.9, 37.1. m/z (EI) 386 (13%, M+•), 322 (20),
266 (100).
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doi:10.1071/CH07336
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S0960-894X(02)00346-3
Synthesis of 1,1-Dioxo-6-phenyl-3-piperidino-1λ6-
[1,2,4]triazolo[2,3-b][1,4,2,6]dithiadiazine 6e
in Absence of Base
A stirred mixture of 3-mercapto-5-phenyl[1,2,4]triazole 5d
(356 mg, 2 mmol), the dichloro compound 1d (640 mg,
2.6 mmol), and DMPU (3 mL) was heated at 80◦C for 24 h. Ethyl
acetate (10 mL) was stirred in, followed by water (20 mL), and
the resulting mixture was stirred vigorously at room temperature
for 1 h. The precipitate was collected by filtration and washed
sequentiallywithwater, ethylacetate, anddiethyletherthendried
to provide the title compound (131 mg, 19%) as a white solid,
mp 240–241◦C. The spectroscopic properties were as described
above.
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Acknowledgements
We thank Ruth Woodgate for technical assistance with chemical synthesis,
Roger Mulder and Jo Cosgriff for assistance with NMR spectroscopy, Carl
[22] J. Mohan, Anupama, Indian J. Chem. 2001, 40B, 54.