N,N-Dialkyl-N′-chlorosulfonyl chloroformamidines in heterocyclic synthesis. part IX.* novel triazolo-fused thiatriazoles and pyrazolo-fused oxathiazines

Article abstract of DOI:10.1071/CH09607

N,N-dialkyl-N′-chlorosulfonyl chloroformamidines 1 reacted with 4-substituted urazoles 2 to give [1,2,4]triazolo[1,2-b] [1,2,3,5]thiatriazoles 3 in a selective 1,2-NN dinucleophilic mode of reaction.The reaction of 1 with N¹-substituted pyrazol-5-ones 4 afforded pyrazolo[4,3-e][1,4,3] oxathiazines 5 via selective 1,3-CCO dinucleophilic substitution. Compounds 3 and 5 were the sole products isolated from the respective reactions and both represent new ring systems. CSIRO 2010.

Full text of DOI:10.1071/CH09607

RESEARCH FRONT
Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2010, 63, 785–791
N,N-Dialkyl-Nꢀ-Chlorosulfonyl Chloroformamidines
in Heterocyclic Synthesis. Part IX.∗ Novel Triazolo-Fused
Thiatriazoles and Pyrazolo-Fused Oxathiazines
Craig M. Forsyth,A Craig L. Francis,B,D Saba Jahangiri,B Andris J. Liepa,B
Michael V. Perkins,C and Anna P. YoungC
ASchool of Chemistry, Monash University, Box 23, Clayton, Vic. 3800, Australia.
BCSIRO Molecular and Health Technologies, Bag 10, Clayton South, Vic. 3169, Australia.
CSchool of Chemistry, Physics and Earth Sciences, Flinders University, PO Box 2100,
Adelaide, SA 5001, Australia.
DCorresponding author. Email: craig.francis@csiro.au
N,N-dialkyl-Nꢀ-chlorosulfonyl chloroformamidines 1 reacted with 4-substituted urazoles 2 to give [1,2,4]triazolo[1,2-b]
[1,2,3,5]thiatriazoles3inaselective1,2-NNdinucleophilicmodeofreaction.Thereactionof 1withN1-substitutedpyrazol-
5-ones 4 afforded pyrazolo[4,3-e][1,4,3]oxathiazines 5 via selective 1,3-CCO dinucleophilic substitution. Compounds 3
and 5 were the sole products isolated from the respective reactions and both represent new ring systems.
Manuscript received: 24 November 2009.
Manuscript accepted: 15 January 2010.
Introduction
from this reaction apparently arise from numerous tautomeric
forms available to N-unsubstituted pyrazol-3-ones.[1]
We recently reported[1] that the reaction between N,N-dialkyl
Nꢀ-chlorosulfonyl chloroformamidines 1 and N-unsubstituted
pyrazol-3-ones produced the previously unknown pyrazolo
[3,2-b][1,2,3,5]oxathiadiazine and pyrazolo[2,3-e][1,4,3,5]
oxathiadiazine ring systems, along with, in minor proportion(s),
one or two trioxo isomers of the rare pyrazolo[1,2-b][1,2,3,5]
thiatriazole ring system (Scheme 1). The four possible products
We were interested in trying to constrain the regiochemical
outcome of this or similar multisite reactions by restricting the
number of tautomeric forms available to the starting dinucleo-
phile. We envisaged that in this way, fewer products would be
created, ratherthanmixturesofseveralisomers.Thefeasibilityof
this approach was explored and this paper details the outcomes.
Results and Discussion
R2N
R1
N
R2
The dichlorides 1a–d were readily prepared[1,2] from sulfuryl
chloride and the corresponding dialkyl cyanamide (Scheme 2).
InplaceofN-unsubstitutedpyrazol-3-ones, whichonreaction
with dichlorides 1 gave mainly 1,3-NCO disubstituted prod-
ucts and little 1,2-NN disubstituted products, we chose to use
4-substituted urazoles 2. These compounds cannot exist as tau-
tomers containing an NH–C–OH moiety and therefore cannot
act as 1,3-NCO dinucleophiles. It is known that 4-phenylurazole
reacts smoothly with acetic anhydride to afford the 1,2-
diacetylated product in almost quantitative yield.[3] Therefore,
CI
CI
N
ϩ
O
S
N
H
O
O
1
R1
R2
N
R2N
O
S
R2
R2N
N
R1
ϩ
ϩ
N
N
N
N
O
S
O
O
O
O
Major
O
Significant
R2N
R1
R2
R2N
R2
R1
1a
1b
Me2N
Et2N
CI
CI
SO2CI2
R2N
R2N
N
N
N
N
S
ϩ
N
R2N
N
O
S
N
N
S
1c
1d
O
N
N
O
O
O
O
O
1
Minor
Minor
Scheme 1.
∗Part VIII, published in Aust. J. Chem. 2010, 63, 659.
Scheme 2. General synthesis of dichlorides 1.
© CSIRO 2010
10.1071/CH09607
0004-9425/10/050785

RESEARCH FRONT
786
C. M. Forsyth et al.
R1 N C O
EtO
HN
R1
O
O
(1) Aq. KOH
(2) Aq. HCI
Benzene
ϩ
HN
H
N
OEt
N
H
H2N
O(3)
O
R1
Ph
4-CI-Ph
3-CI-Ph
1-Naphthyl
Cyclohexyl
Pri
N(3)
O
C(5)
2a
2b
2c
2d
2e
2f
HN
HN
N R1
N(4)
N(6)
C(7)
C(3)
O
2
N(2)
CI(1)
N(8)
S(1)
O(4)
O(1)
Scheme 3. General synthesis of urazoles 2.
O(2)
O
R2N
O
R2N
R1
CI
CI
Pri2NEt
N
HN
N
R1
N
O
C(8)
ϩ
N
N
O
N
HN
DMPU
S
S
O(4)
O
O
O
O
C(7)
1
2
3
N(3)
C(4)
C(9)
Scheme 4.
N(4)
C(3)
C(10)
C(11)
N(5)
Table 1. Synthesis of the [1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazoles 3
N(2)
R1
Product
Yield [%]
C(6)
R2N
N(6)
Me2N (1a)
Et2N (1b)
Ph (2a)
Ph (2a)
3a
3b
50
31
S(1)
O(6)
O(1)
Ph (2a)
3c
3d
3e
60
54
73
N
O(2)
(1c)
Me2N (1a)
4-Cl-Ph (2b)
3-Cl-Ph (2c)
Fig. 1. ORTEP diagrams of 3e and 3h.
N
(1c)
or ethanol. After boiling in these solvents, significant decom-
position was observed by NMR spectroscopy. Nevertheless,
recrystallization to analytical purity was possible from iso-
propanol or from ethanol/chloroform or isopropanol/acetone
mixtures.
1-Naphthyl (2d)
3f
55
N
(1d)
Me2N (1a)
Me2N (1a)
Cyclohexyl (2e)
Pri (2f)
3g
3h
29
16
The structural assignments for 3a–h were confirmed by X-ray
crystallographic analyses of 3e and 3h as typical representatives
(Fig. 1 and Table 3).
we were confident that 4-substituted urazoles 2 would react with
dichlorides 1 through the two nitrogen atoms, N1 and N2.
The 4-substituted urazoles 2a–f were synthesized from
ethyl hydrazinecarboxylate and the appropriate isocyanate
(Scheme 3).[4]
The reaction of dichlorides 1 with 4-substituted ura-
zoles 2 in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone
(dimethylpropylene urea, DMPU), in the presence of Hünig’s
base, readily gave [1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazoles 3,
the first reported representatives of this ring system, as the sole
isolated product (Scheme 4, Table 1).
The [1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazoles 3 were iso-
lated in high purity after simple precipitation from the DMPU-
based reaction mixture (by the addition of ethyl acetate and
water) and washing with dilute hydrochloric acid. The relatively
low yields of diethylamino derivative 3b and alkyl-substituted
compounds 3g and 3h may be simply a result of their greater
solubility in organic solvents. No attempts were made to isolate
further amounts of these products from the mother liquor.
The products 3 were stable, colourless, crystalline solids;
however, we were not able to recrystallize them from methanol
As predicted, ring formation to produce compounds 3 pro-
ceeded via the 1,2-NN dinucleophilic mode of addition.
With a method in hand that selectively gave fused, bicyclic
products arising from 1,2-NN dinucleophilic reaction, we turned
our attention toward attempting to alter the course of the reac-
tion between pyrazol-3-ones and dichlorides 1 so as to obtain
fused cyclic products involving C-substitution. Employing
N1-substituted pyrazol-5-ones, which are substituted at the nitro-
gen atom directly adjacent to the carbonyl group, should block
both of the 1,2-NN and 1,3-NCO modes of reaction and we
expected that this should ensure 1,3-CCO dinucleophilic substi-
tution, because such pyrazolones are well known to acylate at
C4 (and sometimes at N2 or the exocyclic oxygen atom).[5–7]
N-Substituted pyrazolones 4a–e were synthesized from
the appropriate β-ketoesters and monosubstituted hydrazines
(Scheme 5).[8]
Treatment of pyrazolones 4 with dichlorides 1 at 80◦C
in DMPU indeed effected 1,3-CCO dinucleophilic substi-
tution to form 3-dialkylamino-1,1-dioxo-1λ6-pyrazolo[4,3-e]
[1,4,3]oxathiazines 5 (Scheme 6, Table 2). These compounds

RESEARCH FRONT
N,N-Dialkyl-Nꢀ-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis
787
R1, R2
Me, Ph
Me, 2-CI-Ph 4b
R2
4a
O
R1
OEt
R2NHNH2
N
N
Et, Ph
4c
4d
4e
EtOH, Δ
O
O
Me, But
CF3, Me
R1
4
Scheme 5. General synthesis of pyrazolones 4.
O(4)
N(5)
R2
N
C(4)
O
R2N
N
C(3)
N(2)
N(6)
C(7)
N
S
R2N
R2
R1
O
O
CI
CI
O
N
DMPU
5
N
O
ϩ
N
Δ
S
S(1)
O(2)
R1
O(1)
R1
O
N
R2
1
4
N
R2N
N
O
S
O
O
6
Scheme 6.
CI(1)
O(4)
Table 2. Synthesis of the pyrazolo[4,3-e][1,4,3]oxathiazines 5
R2N
R1
R2
Product
5a
Yield [%]
N(5)
N(3)
Me2N (1a)
Me
Me
Ph (4a)
2-Cl-Ph (4b)
61
72
C(4)
5b
N
(1c)
N(6)
C(3)
Me
Et
2-Cl-Ph (4b)
Ph (4c)
5c
56
37
N
(1d)
C(7)
N(2)
C(8)
5d
N
(1c)
S(1)
Me2N (1a)
Et2N (1b)
Me2N (1a)
Et2N (1b)
Me
Me
CF3
CF3
But (4d)
But (4d)
Me (4e)
Me (4e)
5e
5f
5g
5h
20
26
59
34
N
CF3
Me (4e)
5i
50
(1d)
are the first reported representatives of the pyrazolo[4,3-e]
[1,4,3]oxathiazine ring system.
Usually, the pyrazolo[4,3-e][1,4,3]oxathiazines 5 were pre-
cipitated from the reaction mixture in high purity by our
favoured[9] ethyl acetate/water workup procedure. No other
products were isolated. In the case of compound 5a, the whole
reaction mixture was analyzed and extensive chromatography
did not reveal the presence of any additional isomeric products.
The derivatives of the new heterocyclic system described
above were all stable, colourless, crystalline solids unaffected
by recrystallization from alcohols.
O(4)
N(3)
N(5)
C(4)
N(6)
C(3)
N(2)
C(7)
C(8)
Spectroscopic studies alone were not sufficient to distinguish
between the two possible isomeric structures 5 and 6; there-
fore structural assignments for compounds listed in Table 2
were based on X-ray crystallographic analyses of representative
compounds 5a, 5c, and 5f (Fig. 2, Table 3).
S(1)
O(1)
O(2)
Fig. 2. ORTEP diagrams of 5a, 5c, and 5f.

RESEARCH FRONT
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C. M. Forsyth et al.
Table 3. Crystal data and structure refinement for 3e, 3h, 5a, 5c, 5f
3e
3h
5a
5c
5f
CCDC no.
Empirical formula
Formula weight
Crystal system
Space group
Unit cell dimensions
a [Å]
755596
C13H12ClN5O4S
369.79
Monoclinic
P21/n
755595
C8H13N5O4S
275.29
Monoclinic
P21/n
755593
C13H14N4O3S
306.34
Monoclinic
P21/c
755594
C16H17ClN4O3S
380.85
Monoclinic
P21/c
755592
C13H22N4O3S
314.41
Monoclinic
P21/c
10.7866(1)
12.7327(2)
11.8309(2)
90
103.803 (1)
90
1577.96(4)
4
1.557
8.6770(2)
13.4273(4)
10.9685(3)
90
111.7350(10)
90
1187.07(6)
4
1.540
9.2397(3)
16.1650(5)
9.3633(4)
90
103.471(1)
90
1360.02(8)
4
1.496
10.2794(2)
19.924(4)
9.2248(1)
90
114.510(1)
90
1719.0(3)
4
1.472
19.3970(6)
18.0859(7)
9.0451(3)
90
91.449(2)
90
3172.12(19)
8
1.317
b [Å]
c [Å]
α [◦]
β [◦]
γ [◦]
Volume [Å3]
Z
ρ (calc.) [mg m−3
]
μ [mm−1
]
0.404
0.290
0.255
0.368
0.220
Crystal size [mm]
θ range [◦]
Ntotal
0.33 × 0.25 × 0.25
2.30 to 27.50
22431
0.25 × 0.25 × 0.13
2.51 to 27.49
7545
0.30 × 0.30 × 0.25
2.27 to 27.50
16515
0.30 × 0.20 × 0.08
2.04 to 27.50
17351
0.25 × 0.25 × 0.20
2.49 to 27.50
30704
N (Rint
Nobs [I > 2σ(I)]
)
3611 (0.061)
2857
2668 (0.062)
2057
3111 (0.061)
2284
3874 (0.068)
2677
7205 (0.054)
5570
R indices [I > 2σ(I)]
R1
wR2
0.0359
0.0796
0.0618
0.1666
0.0443
0.1049
0.0469
0.1081
0.0499
0.1076
R indices (all data)
R1
wR2
GoF (on F2)
0.0555
0.0888
1.041
0.0811
0.1842
1.031
0.0720
0.1183
1.028
0.0805
0.1263
1.042
0.0696
0.1194
1.045
Ring formation to produce the fused oxathiazines 5 proceeds
such that the carbon atom of 4 reacts with the sulfamoyl chlo-
ride moiety of 1 and the oxygen atom bonds with the amidine
carbon atom. This mode of reaction parallels that observed with
4-hydroxy-2-pyrone derivatives and 1,3-dimethylbarbituric acid
(other compounds with an enolizable methylene group), which
were reported earlier.[10]
the method of Taylor and McKillop.[8] Other materials were
obtained from commercial sources.
General Synthesis Procedure for 6-Substituted
3-Dialkylamino-1,1,5,7-tetraoxo-1λ6-[1,2,4]triazolo
[1,2-b][1,2,3,5]thiatriazoles 3a–i
N,N-Diisopropylethylamine (5 mmol) was added to a stirred
mixture of the 4-substituted urazole 2 (2 mmol), the dichloro
compound 1 (3 mmol), and DMPU (2 mL). The resulting mix-
ture was stirred at room temperature for at least 3 h. Ethyl acetate
(5 mL) was added, followed by water (10 mL). The mixture was
stirred vigorously for at least 10 min. The precipitate was col-
lected and the solid was stirred in dilute hydrochloric acid (2 M,
5 mL) for a few minutes before being filtered and the collected
solid washed sequentially with water, ethyl acetate and diethyl
ether.
Conclusion
The dichloro compounds 1, readily available and versa-
tile 1,3-dielectrophiles, have been shown to react with
4-substituted urazoles 2 via selective 1,2-NN dinucleo-
philic substitution to give 3-dialkylamino-1,1,5,7-tetraoxo-
1λ6-[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazoles 3. Reaction of
dichlorides 1 with N-substituted pyrazolones 4 afforded 3-
dialkylamino-1,1-dioxo-1λ6-pyrazolo[4,3-e][1,4,3]oxathiazines
5, which arise from selective 1,3-CCO dinucleophilic sub-
stitution. Compounds 3 and 5 represent hitherto unreported
heterocyclic ring systems.
The following compounds were prepared by the above
procedure:
3-Dimethylamino-6-phenyl-1,1,5,7-tetraoxo-1λ6-
[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazole 3a
Experimental
Methods and Materials
Obtained as an off-white solid in 50% yield. Recrystallized
from ethanol/chloroform (∼4:1); colourless needles, mp 191.5–
192.5◦C. (Found: C 42.6, H 3.7, N 22.5%; M+• 309.0517.
C11H11N5O4S requires C 42.7, H 3.6, N 22.6%; M+• 309.0526).
δH (400 MHz, CDCl3) 7.55–7.42 (5H, m, ArH), 3.39 (3H, s,
NCH3), 3.25 (3H, s, NCH3). δC (50 MHz, CDCl3) 150.8, 148.8,
148.5, 129.9, 129.7, 129.6, 126.0, 41.8, 40.3. m/z (EI) 309 (42%,
Analytical and spectroscopic methods were described
previously.[1]
The urazoles 2a,[4] 2b,[11] 2c,[11] 2d,[12] 2e,[13] 2f[14] were
all synthesized from ethyl hydrazinecarboxylate and the appro-
priate isocyanate using the procedure of Cookson et al.[4] The
pyrazolones 4c,[15] 4d,[16] and 4e[17] were all prepared from
the appropriate β-ketoester and monosubstituted hydrazine by
M
+•), 190 (100).

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789
3-Diethylamino-6-phenyl-1,1,5,7-tetraoxo-1λ6-
[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazole 3b
CDCl3) 8.04 (1H, d, J 8.2, ArH), 7.96 (1H, d, J 7.3, ArH), 7.72
(1H, dd, J 8.2, 0.7, ArH), 7.64–7.56 (3H, m, ArH), 7.52 (1H, dd,
J 7.3, 1.1, ArH), 3.77 (2H, m, NCH2), 3.74 (2H, m, NCH2), 1.79
(4H, m, 2 × CH2), 1.73 (2H, m, CH2). δC (125 MHz, CDCl3)
149.35, 149.34, 148.8, 134.4, 131.6, 129.2, 128.8, 128.3, 127.2,
127.0, 125.4, 125.3, 121.3, 51.7, 49.6, 25.7, 24.8, 23.4. m/z (EI)
399 (48%, M+•), 230 (41), 169 (100).
Obtained in 31% yield after radial chromatography (50–100%
dichloromethane in light petroleum, then 0–5% ethyl acetate in
dichloromethane) and recrystallization from isopropanol; nacre-
ous plates, mp 170–171◦C. (Found: C 46.2, H 4.7, N 21.0%;
M
M
+• 337.0831. C13H15N5O4S requires C 46.3, H 4.5, N 20.8%;
+• 337.0839). δH (400 MHz, CDCl3) 7.55–7.42 (5H, m, ArH),
6-Cyclohexyl-3-dimethylamino-1,1,5,7-tetraoxo-
3.75 (2H, q, J 7.1, NCH2) 3.61 (2H, q, J 7.2, NCH2), 1.38 (3H,
t, J 7.1, CH3), 1.32 (3H, t, J 7.2, CH3). δC (100 MHz, CDCl3)
149.8, 148.8, 148.2, 129.9, 129.7, 129.6, 126.0, 46.7, 44.7, 13.3,
11.7. m/z (EI) 337 (31%, M+•), 218 (100).
1λ6-[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazole 3g
Obtained as a white solid in 29% yield. Recrystallized from
isopropanol/acetone (∼2:1); colourless plates, mp 184–185◦C.
(Found: C 41.9, H 5.5, N 22.0%; M+• 315.0988. C11H17N5O4S
requires C 41.9, H 5.4, N 22.2%; M+• 315.0996). δH (500 MHz,
CDCl3) 3.89 (1H, tt, J 12.4, 3.9, CHN), 3.33 (3H, s, NCH3),
3.20 (3H, s, NCH3), 2.10–2.00 (2H, m), 1.90–1.76 (4H, m),
1.71–1.65 (1H, m), 1.37–1.14 (3H, m). δC (125 MHz, CDCl3)
151.0, 149.8, 149.3, 54.5, 41.7, 40.1, 28.8, 25.5, 24.7. m/z (EI)
315 (11%, M+•), 233 (94), 190 (52), 83 (72), 71 (100).
3-Pyrrolidin-1-yl-6-phenyl-1,1,5,7-tetraoxo-1λ6-
[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazole 3c
Obtained as a white solid in 60% yield. Recrystallized from
ethanol/chloroform (∼3:2); small, colourless needles, mp 218–
220◦C. (Found: C 46.4, H 3.9, N 20.8%; M+• 335.0676.
C13H13N5O4S requires C 46.6, H 3.9, N 20.9%; M+• 335.0683).
δH (500 MHz, CDCl3) 7.54–7.42 (5H, m, ArH), 3.98 (2H, t, J 7,
NCH2) 3.68 (2H, t, J 7, NCH2), 2.12–2.00 (4H, m, CH2CH2).
δC (125 MHz, CDCl3) 148.6, 148.5, 148.0, 129.8, 129.7, 129.6,
126.0, 52.4, 50.7, 26.1, 24.5. m/z (EI) 335 (45%, M+•), 216
(100).
3-Dimethylamino-6-prop-2-yl-1,1,5,7-tetraoxo-1λ6-
[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazole 3h
Obtained as a white solid in 16% yield. Recrystallized from iso-
propanol/acetone (∼2:1); colourless prisms, mp 189.5–190.5◦C.
(Found: C 35.0, H 4.8, N 25.2%; M+• 275.0679. C8H13N5O4S
requires C 34.9, H 4.8, N 25.4%; M+• 275.0683). δH (500 MHz,
CDCl3) 4.31 (1H, septet, J 6.9, CH), 3.34 (3H, s, NCH3), 3.21
(3H, s, NCH3), 1.47 (6H, d, J 6.9, C(CH3)2). δC (125 MHz,
CDCl3) 151.0, 149.7, 149.3, 47.2, 41.7, 40.1, 19.2. m/z (EI) 275
(40%, M+•), 233 (54), 190 (98), 70 (100).
6-(4-Chlorophenyl)-3-dimethylamino-1,1,5,7-tetraoxo-
1λ6-[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazole 3d
Obtained as
a white solid in 54% yield. Recrystal-
lized from isopropanol/acetone (∼1:1); colourless crys-
tals, mp 210–212◦C. (Found: C 38.5, H 2.9, N 20.3%;
M
+• 343.0127. C11H10ClN5O4S requires C 38.4, H 2.9,
N 20.4%; M+• 343.0137). δH (400 MHz, CDCl3) 7.50 (2H, m,
ArH), 7.41 (2H, m, ArH), 3.39 (3H, s, NCH3), 3.25 (3H, s,
NCH3). δC (125 MHz, CDCl3) 150.7, 148.5, 148.1, 135.9, 129.9,
128.0, 127.1, 41.9, 40.3. m/z (EI) 343/345 (35/14%, M+•), 190
(100).
General Synthesis Procedure for 3-Dialkylamino-1,1-
dioxo-1λ6-pyrazolo[4,3-e][1,4,3]oxathiazines 5
A stirred mixture of the N-substituted pyrazolone 4 (2 mmol), the
dichloro compound 1 (2.5 mmol), and DMPU (2 mL) was heated
at 80◦C for 10–11 h. The mixture was cooled and slowly diluted
with water (10 mL) and then ethyl acetate (5 mL). The mixture
was stirred vigorously for at least 15 min. The precipitate was
collected by filtration and washed sequentially with 5% aqueous
NaOH solution, water and diethyl ether.
6-(3-Chlorophenyl)-3-pyrrolidin-1-yl-1,1,5,7-tetraoxo-
1λ6-[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazole 3e
Obtained as a colourless powder in 73% yield. Recrystallized
from isopropanol/acetone (∼1:1) to give colourless prisms,
mp 217.5–219.5◦C. (Found: C 42.3, H 3.4, N 19.0, S 8.6%;
The following compounds were prepared by the above
procedure:
M
+• 369.0294. C13H12ClN5O4S requires C 42.2, H 3.3, N 18.9,
3-Dimethylamino-1,1-dioxo-7-methyl-5-phenyl-1λ6-
pyrazolo[4,3-e][1,4,3]oxathiazine 5a
S 8.7%; M+• 369.0293). δH (400 MHz, CDCl3) 7.51–7.49 (1H,
m, ArH), 7.48–7.44 (2H, m, ArH), 7.41–7.36 (1H, m, ArH),
3.97 (2H, t, J 6.5, CH2N), 3.69 (2H, t, J 6.5, CH2N), 2.14–
2.01 (4H, m, 2 × CH2). δH (400 MHz, [D6]DMSO) 7.67–7.49
(4H, m, ArH), 3.89 (2H, t, J 6.5, CH2N), 3.54 (2H, t, J 6.5,
CH2N), 1.94 (4H, m, 2 × CH2). δC (100 MHz, CDCl3) 148.2,
148.1, 147.9, 135.3, 130.7, 130.6, 130.1, 126.1, 124.0, 52.4,
50.8, 26.1, 24.5. δC (100 MHz, [D6]DMSO) 148.0, 147.9, 147.3,
133.2, 131.1, 130.8, 129.5, 126.7, 125.5, 52.5, 50.5, 25.4, 23.9.
m/z (EI) 369/371 (41/16%, M+•), 216 (100), 153/155 (24/8), 96
(55). Colourless single crystals suitable for X-ray analysis were
obtained by slow evaporation of an acetone solution.
The reaction mixture was diluted with water only. The result-
ing sticky orange precipitate was collected and dissolved in
dichloromethane. The filtrate was extracted several times with
dichloromethane. The combined extracts were added to the
solution of the precipitate and the whole was washed with
5% aqueous sodium hydroxide solution and then water. The
solvent was removed under reduced pressure. The aqueous
phase slowly yielded additional precipitate after several hours.
All product samples obtained were chromatographed over sil-
ica gel (dichloromethane/light petroleum, 1:1), affording the
title compound in 61% yield. Recrystallized from acetonitrile/
dichloromethane; colourless crystals, mp 240–242◦C (dec.).
(Found: C 51.2, H 4.6, N 18.4; M+• 306.0779. C13H14N4O3S
requires C 51.0, H 4.6, N 18.3%; M+• 306.0781). δH (300 MHz,
CDCl3) 7.60–7.56 (2H, m,ArH), 7.54–7.49 (2H, m,ArH), 7.44–
7.39 (1H, m,ArH), 3.21 (3H, s, NCH3), 3.14 (3H, s, NCH3), 2.54
(3H, s, CH3). δC (75 MHz, CDCl3) 147.9, 145.0, 144.5, 136.3,
6-Naphth-1-yl-3-piperidin-1-yl-1,1,5,7-tetraoxo-
1λ6-[1,2,4]triazolo[1,2-b][1,2,3,5]thiatriazole 3f
Obtained as an off-white solid in 55% yield. Recrystallized from
isopropanol/acetone (∼2:1); colourless prisms, mp 215–216◦C.
(Found: C 54.4, H 4.6, N 17.6%; M+• 399.0990. C18H17N5O4S
requires C 54.1, H 4.3, N 17.5%; M+• 399.0996). δH (500 MHz,

RESEARCH FRONT
790
C. M. Forsyth et al.
129.6, 128.3, 122.1, 100.9, 39.0, 36.6, 13.5. m/z (EI) 306 (24%,
M
requires C 49.7, H 7.1, N 17.8%; M+• 314.1407). δH (500 MHz,
CDCl3) 3.57 (2H, q, J 7, NCH2), 3.49 (2H, q, J 7, NCH2),
2.43 (3H, s, CH3), 1.61 (9H, s, C(CH3)3), 1.27 (6H, t, J 7,
2 × CH3). δC (125 MHz, CDCl3) 147.4, 145.0, 141.3, 100.0,
60.5, 44.8, 42.4, 29.1, 13.9, 13.4, 12.4. m/z (EI) 314 (54%,
+•), 236 (100), 174 (3), 105 (59), 77 (29), 67 (88).
5-(2-Chlorophenyl)-1,1-dioxo-7-methyl-3-pyrrolidin-1-yl-
1λ6-pyrazolo[4,3-e][1,4,3]oxathiazine 5b
M
+•), 216 (43), 99 (35), 67 (100). Crystals suitable for X-
Obtained in 72% yield after column chromatography (silica
gel, dichloromethane). Recrystallized from ethanol; colourless
crystals, mp 242–243◦C (dec.). (Found: C 49.4, H 4.1, N 15.3%;
ray analysis were obtained by slow evaporation of an ethyl
acetate/dichloromethane solution.
M
+• 366.0537. C15H15ClN4O3S requires C 49.1, H 4.1,
N 15.3%; M+• 366.0553). δH (300 MHz, CDCl3) 7.56–7.54 (1H,
m, Ar), 7.49–7.44 (3H, m, Ar), 3.59 (2H, br s, NCH2), 3.39 (2H,
br s, NCH2), 2.53 (3H, s, CH3), 1.96–1.94 (4H, m, CH2CH2).
δC (50 MHz, CDCl3) 146.3, 145.9, 145.2, 133.3, 131.2, 130.7,
130.5, 129.2, 128.0, 100.5, 48.6, 46.6, 25.3, 24.6, 13.6. m/z (EI)
366 (28%, M+•), 272 (12), 270 (28), 150 (13), 139 (18), 67 (100).
3-Dimethylamino-1,1-dioxo-5-methyl-7-trifluoromethyl-
1λ6-pyrazolo[4,3-e][1,4,3]oxathiazine 5g
Obtained as a cream-coloured solid solid in 59% yield. Recrys-
tallized from methanol/chloroform (∼4:1) giving small, white,
woolly needles, mp 280–282◦C. (Found: C 32.4, H 3.0, N 18.6%;
M
M
+• 298.0336. C8H9F3N4O3S requires C 32.2, H 3.0, N 18.8%;
+• 298.0342). δH (400 MHz, CDCl3) 3.91 (3H, s, 5-NCH3),
5-(2-Chlorophenyl)-1,1-dioxo-7-methyl-3-piperidin-1-yl-
3.23 (6H, s, NMe2). δH (400 MHz, [D6]DMSO) 3.87 (3H, s, 5-
NCH3), 3.19 (3H, s, NCH3), 3.09 (3H, s, NCH3). δF (188 MHz,
CDCl3) −57.01. δC (100 MHz, [D6]DMSO) 147.9, 147.4, 132.8
(q, JCF 40.6), 120.2 (q, JCF 269.3), 99.9, 38.8, 36.9, 36.0. m/z
(EI) 298 (100%, M+•).
1λ6-pyrazolo[4,3-e][1,4,3]oxathiazine 5c
Obtained in 56% yield after chromatography (silica gel,
dichloromethane/light petroleum, 1:1). Recrystallized from
ethanol; colourless crystals, mp 243–244◦C (dec.). (Found:
C 50.7, H 4.5, N 14.8%; M+• 380.0698. C16H17ClN4O3S
requires C 50.5, H 4.5, N 14.7%; M+• 380.0704). δH (300 MHz,
CDCl3) 7.59–7.58 (1H, m,Ar), 7.56–7.46 (3H, m,Ar), 3.70 (2H,
br s, NCH2), 3.40 (2H, br s, NCH2), 2.55 (3H, s, CH3), 1.65 (6H,
br s, CH2CH2CH2). δC (50 MHz, CDCl3) 146.4, 146.3, 145.2,
133.5, 131.2, 130.6, 130.5, 129.3, 128.1, 100.6, 47.5, 45.5, 25.6,
24.9, 23.7, 13.6. m/z (EI) 380 (28%, M+•), 272 (15), 270 (40),
150 (17), 139 (21), 111 (26), 67 (100).
3-Diethylamino-1,1-dioxo-5-methyl-7-trifluoromethyl-
1λ6-pyrazolo[4,3-e][1,4,3]oxathiazine 5h
Obtained as colourless crystals in 34% yield; mp 231–233◦C.
(Found:C36.9, H4.2, N17.0%;M+• 326.0651. C10H13F3N4O3S
requires C 36.8, H 4.0, N 17.2%; M+• 326.0655). δH (400 MHz,
CDCl3) 3.89 (3H, s, NCH3), 3.57 (2H, q, J 7, NCH2), 3.55 (2H,
q, J 7, NCH2), 1.32 (3H, t, J 7, CH3), 1.28 (3H, t, J 7, CH3). δF
(188 MHz, CDCl3) −62.99. δC (50 MHz, CDCl3) 146.4, 146.0,
135.3 (q, JCF 41.7), 119.4 (q, JCF 270.2), 100.2, 45.1, 42.8, 35.3,
13.8, 12.2. m/z (EI) 326 (66%, M+•), 98 (100).
1,1-Dioxo-7-ethyl-5-phenyl-3-pyrrolidin-1-yl-1λ6-
pyrazolo[4,3-e][1,4,3]oxathiazine 5d
Obtained as a light grey solid in 37% yield after sequential
boiling with isopropanol and trituration with dichloromethane.
Recrystallized from ethanol; fine, colourless needles, mp 216.5–
217.5◦C. (Found: C 55.6, H 5.3, N 16.5%; M+• 346.1090.
C16H18N4O3S requires C 55.5, H 5.2, N 16.2%; M+• 346.1094).
δH (500 MHz, CDCl3) 7.63–7.59 (2H, m, Ar), 7.53–7.48 (2H,
m, Ar), 7.42–7.37 (1H, m, Ar), 3.65 (2H, t, J 6.6, NCH2), 3.58
(2H, t, J 6.6, NCH2), 2.93 (2H, q, J 7.6, CH2), 2.07–1.96 (4H, m,
CH2CH2), 1.42 (3H, t, J 7.6, CH3). δC (125 MHz, CDCl3) 150.1,
146.0, 145.0, 136.5, 129.6, 128.1, 121.9, 100.5, 48.7, 46.8, 25.5,
24.7, 21.9, 12.4. m/z (EI) 346 (24%, M+•), 250 (87), 105 (38),
81 (100).
1,1-Dioxo-5-methyl-3-piperidin-1-yl-7-trifluoromethyl-
1λ6-pyrazolo[4,3-e][1,4,3]oxathiazine 5i
Obtained as a very pale pink solid in 50% yield. Recrys-
tallized from methanol/chloroform (∼4:1); small, colourless
needles, mp 276–277◦C. (Found: C 39.1, H 4.1, N 16.8%;
M
+• 338.0649. C11H13F3N4O3S requires C 39.1, H 3.9,
N 16.6%; M+• 338.0655). δH (500 MHz, CDCl3) 3.90 (3H, s,
NCH3), 3.73 (2H, br s, NCH2), 3.68 (2H, br s, NCH2), 1.72 (6H,
br s, 3 × CH2). δF (188 MHz, CDCl3) −62.99. δC (125 MHz,
CDCl3) 146.4, 145.4, 135.5 (q, JCF 41.8), 119.3 (q, JCF 270.2),
100.2, 47.7, 45.7, 35.4, 25.7, 24.9, 23.7. m/z (EI) 338 (45%,
M
+•), 110 (100).
5-tert-Butyl-3-dimethylamino-1,1-dioxo-7-methyl-
1λ6-pyrazolo[4,3-e][1,4,3]oxathiazine 5e
X-ray Crystallography
Obtained in 20% yield after recrystallization from aqueous
isopropanol; flat, colourless needles, mp 206–208◦C. (Found:
C 46.4, H 6.3, N 19.8%; M+• 286.1089. C11H18N4O3S requires
C 46.1, H 6.3, N 19.6%; M+• 286.1094). δH (500 MHz, CDCl3)
3.20 (3H, s, NCH3), 3.19 (3H, s, NCH3), 2.43 (3H, s, CH3), 1.61
(9H, s, C(CH3)3). δC (125 MHz, CDCl3) 148.3, 145.0, 141.2,
99.8, 60.6, 39.1, 36.8, 29.1, 13.4. m/z (EI) 286 (45%, M+•), 216
(48), 71 (37), 67 (100).
General methods were described previously.[1] Crystals of
5f have two independent molecules in the unit cell.
Both molecules are essentially identical, differing only in
orientation of the Et groups on the NEt2 fragment. CCDC
755592–755596 contain the supplementary crystallographic
data for this paper. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
www.CCDC.cam.ac.uk/data_request/cif.
5-tert-Butyl-3-diethylamino-1,1-dioxo-7-methyl-
1λ6-pyrazolo[4,3-e][1,4,3]oxathiazine 5f
Acknowledgements
Obtained asacolourless solidin26% yield after chromatography
(silica gel, 5% ethyl acetate in dichloromethane). Recrystal-
lized from isopropanol; colourless plates, mp 187.5–189◦C.
(Found: C 49.8, H 6.9, N 17.7%; M+• 314.1402. C13H22N4O3S
We thank Ms Katarina Johansson and Mrs Ruth Woodgate for techni-
cal assistance, Dr Roger Mulder and Dr Jo Cosgriff for assistance with
NMR spectroscopy, and Mr Carl Braybrook and Dr Jo Cosgriff for mass
spectrometry.

RESEARCH FRONT
N,N-Dialkyl-Nꢀ-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis
791
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