N,N-dialkyl-N′-chlorosulfonyl chloroformamidines in heterocyclic synthesis. Part VIII. Novel pyrazolo-fused oxathiadiazines and thiatriazoles

Article abstract of DOI:10.1071/CH09581

N,N-dialkyl-N′-chlorosulfonyl chloroformamidines 1 reacted with pyrazol-3-ones 2 under a variety of conditions to give pyrazolo[2,3-e][1,2,3,5] oxathiadiazine dioxides 3 and pyrazolo[3,2-b][1,4,3,5]oxathiadiazine dioxides 5, and frequently, one or both of pyrazolo[1,2-b][1,2,3,5]thiatriazole 1,1,5-trioxides 4 and 1,1,7-trioxides 6. In all reactions, the pyrazolo[3,2-b][1,4,3,5]oxathiadiazine 5 was the major product, with the pyrazolo[2,3-e][1,2,3,5]oxathiadiazine 3 being a significant product in the absence of base. Prior to our recent work, the core ring systems of compounds 3 and 5 had not been reported and compounds 4 and 6 are new derivatives of a rare ring system. CSIRO 2010.

Full text of DOI:10.1071/CH09581

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2010, 63, 659–668
N,N-Dialkyl-Nꢀ-Chlorosulfonyl Chloroformamidines in
Heterocyclic Synthesis. Part VIII.∗ Novel Pyrazolo-Fused
Oxathiadiazines and Thiatriazoles
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 pyrazol-3-ones 2 tunder a variety of conditions to give
pyrazolo[2,3-e][1,2,3,5]oxathiadiazine dioxides 3 and pyrazolo[3,2-b][1,4,3,5]oxathiadiazine dioxides 5, and frequently,
one or both of pyrazolo[1,2-b][1,2,3,5]thiatriazole 1,1,5-trioxides 4 and 1,1,7-trioxides 6. In all reactions, the pyrazolo[3,2-
b][1,4,3,5]oxathiadiazine 5 was the major product, with the pyrazolo[2,3-e][1,2,3,5]oxathiadiazine 3 being a significant
product in the absence of base. Prior to our recent work, the core ring systems of compounds 3 and 5 had not been reported
and compounds 4 and 6 are new derivatives of a rare ring system.
Manuscript received: 6 November 2009.
Manuscript accepted: 10 December 2009.
R2N
R2N
Introduction
Cl
Cl
SO2Cl2
1a
1b
Me2N
Et2N
In a series of recent reports, we have demonstrated the
facility with which N,N-dialkyl Nꢀ-chlorosulfonyl chlorofor-
mamidines 1 provide uncommon or new heterocyclic ring
systems. For example, 1 reacted with hydrazine derivatives to
afford novel [1,2,3,5]thiatriazole dioxides.[1] Various 2-amino-
1-azaheterocycles provided a range of fused [1,2,4,6]thiatriazine
dioxides[2–4] and 2-mercapto-1H-azaheterocycles gave fused
[1,4,2,6]dithiadiazine dioxides.[5] A logical extension of the
above methodology for creating six-membered rings would
be to employ 2-hydroxy-1H-azaheterocycles in similar reac-
tions to produce fused oxathiadiazine derivatives. We envisaged
that pyrazol-3-ones 2 would represent a suitable candidate
2-hydroxy-1H-azaheterocyclic system, because these com-
pounds have been shown to act as 1,3-NCO dinucleophiles in
reactions with dielectrophiles to produce cyclic products.[6,7]
However, these known ambident nucleophiles can also react as
1,2-NN dinucleophiles with dielectrophiles to produce fused
heterocycles.[8,9] We were interested in studying the ability of
pyrazol-3-ones 2 to condense with the dichloro compounds 1
and determining the mode(s) of that reaction. This paper reports
the results from our examination.
N
O
R2N
N
S
1c
N
O
1
Scheme 1. General synthesis of dichlorides 1.
R1, R2
R1
N
R2
R2
Me, H
Prn, H
2a
2b
H2NNH2
R1
OEt
EtOH, ∆
O
Me, Me
(CH2)4
2c
2d
2e
N
H
2
O
O
Ph, H
Scheme 2. General synthesis of pyrazolones 2.
Pyrazol-3-ones 2a–e were synthesized from cyclocondensa-
tion of appropriate β-ketoesters and hydrazine according to a
well-established literature procedure (Scheme 2).[11]
The reaction of dichlorides 1 with pyrazol-3-ones 2 was
examined under a variety of conditions: (A) at 80◦C in 1,3-
Results and Discussion
The dichlorides 1a–c were readily prepared[10] from sulfuryl
dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone
(dimethyl-
propylene urea, DMPU); (B) at ambient temperature in DMPU
chloride and the corresponding dialkyl cyanamide (Scheme 1).
with N,N-diisopropylethylamine (Hünig’s base); (C) at ambient
*Part VII, Aust. J. Chem. 2008, 61, 785.
© CSIRO 2010
10.1071/CH09581
0004-9425/10/040659

660
C. M. Forsyth et al.
R2N
R1
N
R2
Cl
Cl
N
O
ϩ
O
S
N
H
O
1
2
R1
R1
O
R2
O
R2
R2
R1
N
R2N
O
S
R2
R2N
R2N
N
R2N
N
S
R1
ϩ
N
N
S
ϩ
ϩ
N
N
N
N
N
O
N
N
S
O
O
O
O
O
O
O
O
3
4
5
6
Scheme 3.
Table 1. Synthesis of the fused heterocycles 3, 4, 5, and 6
Method A: dimethylpropylene urea (DMPU)/80◦C; Method B: Pri2NEt/DMPU; Method C: KHCO3(aq)/C6H6/Bun4NHSO4; Method D: Et3N/CH2Cl2
R2N
R1
R2
Method
Products (yields [%])
3
4
5
6
Me2N (1a)
Me
Me
H (2a)
H (2a)
A
A
3a (22)
–
5a (29)
–
N
3b (14)
4bA (3)
5b (22)
–
(1c)
Me2N (1a)
Et2N (1b)
Prn
Prn
H (2b)
H (2b)
B
C
3c (24)
3d (8)
4c (2)
4d (2)
5c (34)
5d (60)
–
–
N
Prn
H (2b)
B
3eA[12] (2)
4e (2)
5e (13)
–
(1c)
Me2N (1a)
Et2N (1b)
Me2N (1a)
Me
Me
Me (2c)
Me (2c)
–(CH2)4– (2d)
B
A
A
C
B
B
C
3fA (7)
3g (13)
3hA (17)
–
–
–
5fA (52)
5gA[13] (26)
5hA (23)
5hA (40)
5iA (37)
5jA (47)
5jA (58)
6f (11)
–
4hA (6)
6hA[14] (17)
–
–
–
–
–
Et2N (1b)
Et2N (1b)
–(CH2)4– (2d)
H (2e)
3iA (2)
3j (1)
6iA (17)
Ph
Ph
–
–
3j (1)
N
H (2e)
D
3k (2)
–
5kA (16)
–
(1c)
AX-ray crystal structure obtained.
temperature in benzene/aqueous potassium bicarbonate/
tetrabutylammonium hydrogen sulfate; and (D) at ambient tem-
perature in dichloromethane with triethylamine (see Table 1).
Usually, these reactions provided 4-dialkylamino-2,2-dioxo-
2λ6-pyrazolo[2,3-e][1,2,3,5]oxathiadiazines 3 and 3-dialkyl-
amino-1,1-dioxo-1λ6-pyrazolo[3,2-b][1,4,3,5]oxathiadiazines
5, and frequently, one or both of 3-dialkylamino-1,1,5-trioxo-
Owing to the lack of contiguous NMR-responsive nuclei in
the core heterocyclic systems of products 3, 4, 5, and 6, X-ray
structuralstudiesofseveralrepresentativecompoundswerecriti-
cal in confirming the exact connectivity of the atoms constituting
the heterocyclic cores. Some of the structures obtained from the
X-ray studies are shown in Figs 1–4. Crystal data and structure
refinement for all compounds studied by X-ray diffraction can
be found inTable 2 in the Experimental section, except for 3e,[12]
5g,[13] and 6h,[14] which were published previously.
1λ6-pyrazolo[1,2-b][1,2,3,5]thiatriazoles
4
and 3-dialkyl-
amino-1,1,7-trioxo-1λ6-pyrazolo[1,2-b][1,2,3,5]thiatriazoles 6
(Scheme 3, Table 1). The isomeric reaction products were
separated by chromatography over silica gel.
Prior to our work in this area,[12–14] the pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine and pyrazolo[3,2-b][1,4,3,5] oxathia-
diazine ring systems of compounds 3 and 5 had not been
reported. The minor products, 3-dialkylamino-pyrazolo[1,2-b]
[1,2,3,5]thiatriazole trioxides 4 and 6, are new derivatives of a
rare ring system.[15–17]
The structural assignments were aided by consistent trends
in physical and spectral properties. The order of elution of
the isomers during normal-phase silica gel chromatography
was consistently 3, 4, 5, and then 6. The pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazines 3 were always the most soluble, the
most mobile inTLC and gave strongly absorbing spots under UV
Under all conditions employed, the pyrazolo[3,2-b][1,4,3,5]
oxathiadiazine 5 was the major product, with the pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine 3 usually appearing as a significant prod-
uct in the absence of base. The other two products, pyrazolo
[1,2-b][1,2,3,5]thiatriazoles 4 and 6, were only isolated in minor
amounts on some occasions.
The new fused, bicyclic products 3, 4, 5, and 6 described
above were stable, colourless, crystalline solids, unaffected by
recrystallization from alcohols. Compounds 4d and 5d were
stable, colourless oils.

Novel Pyrazolo-Fused Oxathiadiazines and Thiatriazoles
661
O5
C7
N6
N3
C8
C5
N5
N4
N4
C6
C7
C3
C9
O1
C4
N2
N8
N3
S2
S1
O3
O1
O2
O2
3f
4b
C7
C8
O5
N6
N3
C9
C5
N5
N4
N4
C6
C7
C10
C3
C4
N3
N2
O1
N8
S1
S2
O1
O2
3h
Fig. 1. ORTEP diagrams of 3f and 3h.
4h
Fig. 2. ORTEP diagrams of 4b and 4h.
light. The pyrazolo[1,2-b][1,2,3,5]thiatriazole 1,1,5-trioxides 4
were also visualized satisfactorily under UV light, but most of
the major products 5 (and the other minor products 6) were not
easily seen using this method or other common TLC visualiza-
tion agents including potassium permanganate and anisaldehyde
(vanillin) dips. Interestingly, some of compounds 5 responded
to ninhydrin to give pink or purple coloured products following
TLC, although they contain only tertiary amino groups.
experiments with all compounds 6, a relatively strong nuclear
Overhauser effect (NOE) was observed between the methyl or
methylene groups immediately adjacent to the nitrogen atom of
the dialkylamino substituent and the nearest hydrogen-bearing
substituent on C5. In similar experiments with compounds 3, 4,
and 5, no such NOEs were observed. The relatively close prox-
imity of these hydrogen atoms in compound 6i can be seen in
Fig. 4 (C5 and C12).
In addition to the characteristics described above, there were
consistent trends in 1H NMR spectral properties that distin-
guished each of pyrazolo[2,3-e][1,2,3,5]oxathiadiazines 3 and
pyrazolo[1,2-b][1,2,3,5]thiatriazoles 6 from the other isomers.
The methyl or methylene groups immediately adjacent to the
nitrogen atom of the amine function were non-equivalent in all
derivatives 3 by ∼0.4–0.6 ppm, whereas for all other isomers,
the difference was <0.15 ppm. The reasons for this difference
are unclear; however, the phenomenon allowed clear distinction
of products 3. In 500-MHz gradient-selected nuclear Over-
Ring formation to produce the major products 5 proceeds
such that the oxygen atom of 2 bonds with the amidine carbon
atom of 1 and N2 reacts with the sulfamoyl chloride moiety.
The other significant reaction product 3 results from N2 of the
pyrazolone bonding with the amidine carbon atom of 1 and the
oxygen reacting with the sulfamoyl chloride moiety.
The N-unsubstituted pyrazol-3-ones 2 provide a plethora
of opportunities for tautomerism, with no fewer than eight
tautomers being possible, but in fact four tautomers 2A–D pre-
dominate (Fig. 5).[7,18–21] In non-polar solvents, there is mainly
an equilibrium between the CH and the OH tautomers, in dipolar
1
hauser effect correlation spectroscopy (NOESY) 2D H NMR

662
C. M. Forsyth et al.
O4
C5
N3
C4
C3
N2
C6
N8
N7
S1
O2
O1
5h
O3
C5
N3
C4
C3
C6
N8
N1
N7
S1
O2
O1
5k
Fig. 3. ORTEP diagrams of 5h and 5k.
R1
N
R1
R1
N
R1
R2
R2
OH
R2
OH
R2
C13
C6
HN
HN
C12
O
O
N
H
N
N
H
N
H
C5
C7
C8
2A
2B
2C
2D
C14
CH form
OH form
OH form
NH form
N3
C11
Fig. 5. Tautomers of N-unsubstituted pyrazolones 2.
N4
C15
C3
C10
C9
reacted as either a 1,3-NCO dinucleophile or as a 1,2-NN
dinucleophile in reactions with some 1-alkynyl Fischer carbene
complexes. The formation of the four products was attributed to
the dominant tautomeric forms available to the N-unsubstituted
pyrazolones.[21]
Nevertheless, the tautomers are rapidly interchangeable and
according to the literature, the outcome of acylation of the ring
atoms of pyrazol-3-ones with acid chlorides depends on the type
of substitution on the pyrazol-3-one ring; C-, N-, and O-acylation
are all observed.[18,22,23] Acylation of N-unsubstituted pyra-
zolones with such agents as acetyl chloride, benzoyl chloride and
arylsulfonyl chlorides occurs readily to give 1-acyl-2-pyrazolin-
5-ones as the usual products.[18]
N2
N10
S1
O9
O1
6i
Fig. 4. ORTEP diagram of 6i.
O2
aprotic solvents, the OH tautomers predominate, whereas protic
solvents favour a mixture of the OH and the NH tautomers.[19]
A recent report[21] described the formation of all four pos-
sible cyclic products that resulted when pyrazol-3-ones 2a–d
The results obtained during this study are largely con-
sistent with outcomes that could have been predicted based
on literature precedents. However, our earlier papers in this

Novel Pyrazolo-Fused Oxathiadiazines and Thiatriazoles
663
series[1–5,24] demonstrated the greater electrophilicity of the
amidinylchloridemoietyrelativetothesulfamoylchloridegroup
in dichlorides 1, and this factor guides regiochemical selectivity
during cyclization reactions. Thus, with N-unsubstituted pyra-
zolones 2, it would have been expected that reactions with 1
would afford fused oxathiadiazines 3 as the major products.
Therefore, it was somewhat surprising to find that the major
cyclization pathway seemingly included an initial reaction by
the sulfamoyl chloride, leading to the isomeric products 5.
The reason for this apparent reversal of selectivity is unclear,
although an alternative explanation may also apply. There may
still be a preference for the amidinyl chloride in all cases, but
the nucleophilicity of the ambident nucleophile changes from
nitrogen (to give 3) to oxygen (to give 5).
N,N-Dialkyl-Nꢀ-chlorosulfonyl Chloroformamidines 1a–c
Prepared essentially by literature procedures.[1,10] Thus, the
appropriate dialkylcyanamide (0.1 mol) was added dropwise to
cooled (ice/water external bath) and stirred sulfuryl chloride
(0.2 mol). The mixture was stirred overnight (ice bath replen-
ished) and the excess of sulfuryl chloride was removed by rotary
evaporation (2 h, 60◦C, NaOH trap). The crude products were
stored under nitrogen and used without further purification. The
deterioration of these compounds and substantial losses dur-
ing attempted purification outweighed the benefits of increased
purity.
N,N-Dimethyl-Nꢀ-chlorosulfonyl Chloroformamidine 1a
Obtained as a pale yellow, low-mp solid (92% crude yield).
δH (300 MHz) 3.40 (3H, s, NCH2), 3.33 (3H, s, NCH2). δC
(75 MHz) 151.5, 41.9, 41.6.
Conclusion
N,N-Diethyl-Nꢀ-chlorosulfonyl Chloroformamidine 1b
The dichloro compounds 1, versatile 1,3-dielectrophiles,
have been shown to react with readily available pyrazol-
3-ones 2 to afford dioxo derivatives of the pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine and pyrazolo[3,2-b][1,4,3,5] oxathiadi-
azine ring systems, compounds 3 and 5, respectively. Prior to our
work in this area, these ring systems had not been reported. Basic
reaction conditions favoured formation of the pyrazolo[3,2-b]
[1,4,3,5]oxathiadiazine product 5. The minor products, 3-
dialkylamino-pyrazolo[1,2-b][1,2,3,5]thiatriazole trioxides 4
and 6, are new derivatives of a rare ring system.
Obtained as a yellow, sticky, low-mp solid (92% crude yield). δH
(300 MHz) 3.71 (2H, q, J 4.7, NCH2), 3.69 (2H, q, J 4.7, NCH2),
1.36 (3H, t, J 7.4, CH3), 1.30 (3H, t, J 7.4, CH3). δC (75 MHz)
152.6, 47.9, 47.4, 13.0, 12.0.
N,N-Pentamethylene-Nꢀ-chlorosulfonyl
Chloroformamidine 1c
Obtained as a pale yellow, low-mp solid (99% crude yield).
δH (300 MHz) 3.88 (4H, q, J 5.8, 2 × NCH2), 1.73 (6H, br s,
3 × CH2). δC (75 MHz) 152.0, 51.0, 50.8, 26.0, 25.4, 23.4.
Experimental
General Synthesis Procedures for 4-Dialkylamino-
2,2-dioxo-2λ6-pyrazolo[2,3-e][1,2,3,5]oxathiadiazines 3,
3-Dialkylamino-1,1,5-trioxo-1λ6-pyrazolo[1,2-b][1,2,3,5]
thiatriazoles 4, 3-Dialkylamino-1,1-dioxo-1λ6-pyrazolo[3,2-b]
[1,4,3,5]oxathiadiazines 5, and 3-Dialkylamino-1,1,7-
trioxo-1λ6-pyrazolo[1,2-b][1,2,3,5]thiatriazoles 6
Methods and Materials
Melting points were determined using a Reichert hot-stage
microscope or a Gallenkamp MPD350.BM2.5 apparatus and are
uncorrected.AnalyticalTLC was carried out on Merck Kieselgel
60 F254 silica aluminium-backed sheets. Developed plates were
visualized with either UV light (254 nm), cold 5% (w/v) aque-
ous FeCl3 dip (good for pyrazolones, which gave a red, brown, or
purple immediate colouration), ninhydrin dip (0.75 g ninhydrin,
2.5 mL acetic acid, 250 mL of 95% ethanol), 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 on a Varian Gemini 300 at 300 MHz or
a Bruker AV400 at 400 MHz. 13C NMR spectra were recorded
at room temperature on a Bruker AC-200 at 50 MHz, a Varian
Gemini 300 at 75 MHz, a Bruker AV400 at 100.6 MHz, or a
Bruker DRX500 at 125.75 MHz. Deuterochloroform was used
as solvent and also as an internal lock. Electron impact (EI)
mass spectra were recorded on a ThermoQuest MAT95XL mass
spectrometer using ionization energy of 70 eV. Only the major
fragments are given with their relative abundances shown in
parentheses. Accurate mass measurements were obtained with
a resolution of 5000–10000 using perfluorokerosene as the
internal reference. Microanalyses were performed at the Camp-
bell Microanalytical Laboratory, University of Otago, Dunedin,
New Zealand.
Method A
A stirred mixture of pyrazolone 2 (5 mmol) and dichloro
compound 1 (6.5 mmol) in DMPU (4 mL) was heated to 80◦C
for 4–9 h (reaction progress monitored using TLC (cold 5% aq.
FeCl3 dip)). The reaction mixture was allowed to cool, diluted
slowly with water (20 mL), stirred for several hours and the
resulting precipitate was filtered under suction, washed with
water, and dried under vacuum. The mother liquor was allowed
to stand overnight and any additional precipitate was treated as
described above. If no precipitate formed, an extractive workup
was carried out with dichloromethane. The crude product mix-
ture was chromatographed over silica gel and the products were
recrystallized.
Method B
A stirred solution of pyrazolone 2 (5 mmol) and dichloro
compound 1 (6.5 mmol) in DMPU (4 mL) was warmed gently
to dissolve the dichloro compound. The resulting mixture was
cooled with an ice/water bath and N,Nꢀ-diisopropylethylamine
(13 mmol) was added dropwise. Stirring was continued
overnight (reaction progress monitored using TLC (cold 5% aq.
FeCl3 dip)). The mixture was diluted slowly with water (20 mL),
stirred for several hours and the resulting precipitate was col-
lected, washed with water and dried under vacuum. The mother
liquor was adjusted to pH 3 by dropwise addition of HCl (conc.),
allowed to stand overnight and any additional precipitate was
The pyrazolones 2a,[11,25,26] 2b,[11] 2c,[26] 2d,[26] and
2e[11,26] were all prepared from the appropriate β-ketoester
and hydrazine using the procedure of Taylor and McKillop.[11]
Other materials were obtained from commercial sources. Light
petroleum refers to a fraction with boiling range 60–80◦C.

664
C. M. Forsyth et al.
treated as described above. If no precipitate formed, an extrac-
tive workup was carried out with dichloromethane. The crude
product mixture was chromatographed over silica gel and the
products were recrystallized.
270.0777. C10H14N4O3S requires C 44.4, H 5.2, N 20.7%; M+•
270.0781). δH (300 MHz) 5.83 (1H, s, C=CH), 4.30 (2H, br s,
NCH2), 3.74 (2H, br s, NCH2), 2.26 (3H, s, N=CCH3), 1.72
(6H, br s, 3 × CH2). δC (75 MHz) 153.1, 150.9, 146.6, 93.3,
50.9, 48.4, 26.0, 25.3, 23.7, 14.6. m/z (EI) 270 (1%, M+•), 206
(67), 109 (86), 84 (100).
Method C
The dichloro compound 1 (6.5 mmol) was added to a stirred
mixture of pyrazolone 2 (5 mmol), KHCO3 (4 g), water (10 mL),
Bun4NHSO4 (0.1 g), and benzene (10 mL). The reaction mix-
ture was warmed gently to dissolve the dichloro compound and
stirred overnight at room temperature. The aqueous layer was
removed. The precipitate and benzene layer were washed with
5% aq. NaOH (2 × 10 mL) and water (2 × 10 mL) and then evap-
orated under reduced pressure. The pH of the aqueous layer was
adjusted to pH 3 by dropwise addition of HCl (conc.) and allowed
to stand overnight. Any additional precipitate was treated as
above. The crude product mixture was chromatographed over
silica gel and the products were recrystallized.
4b (3% yield): Recrystallized from isopropanol; colourle+ss•
crystals, mp 171–173◦C. (Found: C 44.5, H 5.3, N 20.9; M
270.0781. C10H14N4O3S requires C 44.4, H 5.2, N 20.8%; M+•
270.0781). δH (300 MHz) 5.48 (1H, s, C=CH), 3.67 (2H, t, J 5.4,
NCH2), 3.61 (2H, t, J 5.1, NCH2), 2.39 (3H, s, N=CCH3), 1.72
(6H, br s, 3 × CH2). δC (75 MHz) 163.9, 160.5, 149.0, 106.0,
51.9, 48.8, 25.9, 24.9, 23.4, 13.5. m/z (EI) 270 (2%, M+•), 206
(67), 109 (85), 84 (100).
5b (22% yield): Recrystallized from isopropanol; colourle+ss•
needles, mp 166–168◦C. (Found: C 44.5, H 5.4, N 20.3; M
270.0780. C10H14N4O3S requires C 44.4, H 5.2, N 20.7%; M+•
270.0781). δH (300 MHz) 5.71 (1H, s, C=CH), 3.66 (4H, br s,
CH2NCH2), 2.26 (3H, s, N=CCH3), 1.67 (6H, br s, 3 × CH2).
δC (75 MHz) 151.9, 147.9, 147.3, 89.4, 47.1, 45.8, 25.3, 24.7,
23.3, 14.3. m/z (EI) 270 (100%, M+•), 149 (19), 135 (16), 111
(54), 110 (58), 68 (92).
Method D
A stirred mixture of pyrazolone 2 (5 mmol) and dichloro com-
pound 1 (6.5 mmol) in dichloromethane (5 mL) was warmed
gently to dissolve the dichloro compound and then cooled in
an ice/water bath. Triethylamine (13 mmol) was added drop-
wise and the resulting mixture was stirred at room temperature
for 5 h (reaction progress monitored using TLC (cold 5% aq.
FeCl3 dip)). The reaction mixture was diluted slowly with water
(20 mL) and treated as for Method B.
4-Dimethylamino-2,2-dioxo-7-propyl-2λ6-pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine 3c, 3-Dimethylamino-7-propyl-
1,1,5-trioxo-1λ6-pyrazolo[1,2-b][1,2,3,5]thiatriazole 4c,
and 3-Dimethylamino-6-propyl-1,1-dioxo-1λ6-
pyrazolo[3,2-b][1,4,3,5]oxathiadiazine 5c
The following compounds were prepared by the above
procedures.
Method B. No precipitate after addition of ethyl acetate (6 mL)
to the stirred reaction mixture followed by ether (20 mL) and pH
correction to 3. The aqueous layer was extracted with dichloro-
methane. The combined organic phases were washed with
water, dried, and concentrated under reduced pressure to yield
a dark red, viscous oil. Purification by column chromatography
(50–100% dichloromethane in light petroleum, then 0–5% ethyl
acetate in dichloromethane) afforded three products:
3c (24% yield): Recrystallized from isopropanol; colourless
needles, mp 78–80◦C. (Found: C 42.0, H 5.4, N 21.9; M+•
258.0773. C9H14N4O3S requires C 41.9, H 5.5, N 21.7%; M+•
258.0781). δH (300 MHz) 5.85 (1H, s, C=CH), 3.65 (3H, br s,
NCH3), 3.25 (3H, br s, NCH3), 2.58 (2H, t, J 7.5, CH2CH2CH3),
1.67 (2H, tq, J 7.5, 7.5, CH2CH2CH3), 0.97 (3H, t, J 7.4,
CH2CH2CH3). δC (75 MHz) 157.4, 150.8, 148.0, 92.4, 42.0,
40.4, 31.0, 21.4, 13.7. m/z (EI) 258 (100%, M+•), 194 (23), 151
(24), 139 (64), 138 (57).
4c (2% yield): Recrystallized from isopropanol; colourless
crystals, mp 66–67◦C. (Found: C 42.0, H 5.6, N 21.6; M+•
258.0778. C9H14N4O3S requires C 41.9, H 5.6, N 21.7%; M+•
258.0781). δH (300 MHz) 5.48 (1H, s, C=CH), 3.32 (3H, br s,
NCH3), 3.17 (3H, br s, NCH3), 2.68 (2H, t, J 7.5, CH2CH2CH3),
1.76 (2H, tq, J 7.4, 7.4, CH2CH2CH3), 1.04 (3H, t, J 7.4,
CH2CH2CH3). δC (75 MHz) 165.1, 164.6, 150.8, 105.0, 42.0,
39.6, 29.7, 20.7, 13.5. m/z (EI) 258 (99%, M+•), 194 (26), 166
(20), 152 (23), 139 (70), 138 (62), 69 (100), 67 (77).
5c (34% yield): Recrystallized from isopropanol; colourless
woolly needles, mp 87.5–88.5◦C. (Found: C 42.0, H 5.5, N
22.0; M+• 258.0772. C9H14N4O3S requires C 41.9, H 5.6, N
21.7%; M+• 258.0781). δH (400 MHz) 5.76 (1H, s, C=CH),
3.22 (3H, br s, NCH3), 3.21 (3H, br s, NCH3), 2.63 (2H, t, J 7.5,
CH2CH2CH3), 1.68 (2H, tq, J 7.4, 7.4, CH2CH2CH3), 0.97 (3H,
t, J 7.4, CH2CH2CH3). δC (75 MHz) 156.0, 149.4, 147.1, 88.4,
4-Dimethylamino-2,2-dioxo-7-methyl-2λ6-pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine 3a and 3-Dimethylamino-
1,1-dioxo-6-methyl-1λ6-pyrazolo[3,2-b][1,4,3,5]
oxathiadiazine 5a
Method A. Column chromatography mobile phase: 5% ethyl
acetate/dichloromethane.
3a (22% yield): Recrystallized from isopropanol; colourless
crystals, mp 134–136◦C. (Found: C 36.6, H 4.4, N 24.6; M+•
230.0466. C7H10N4O3S requires C 36.5, H 4.4, N 24.3%; M+•
230.0468). δH (300 MHz) 5.83 (1H, s, C=CH), 3.63 (3H, br s,
NCH3), 3.22 (3H, s, NCH3), 2.26 (3H, s, CH3). δC (75 MHz)
153.1, 150.7, 147.8, 93.1, 41.9, 40.2, 14.5. m/z (EI) 230 (95%,
M
+•), 166 (49), 123 (43), 111 (45), 110 (57), 70 (55), 69 (100),
68 (92).
5a (29% yield): Recrystallized from methanol; small, colour-
less, flat needles, mp 224–226◦C. (Found: C 36.8, H 4.5, N 24.6;
M+• 230.0471. C7H10N4O3S requires C 36.5, H 4.4, N 24.3%;
M+• 230.0468). δH (300 MHz) 5.74 (1H, s, C=CH), 3.22 (3H,
s, NCH3), 3.21 (3H, s, NCH3), 2.32 (3H, s, CH3). δC (75 MHz)
152.18, 149.6, 147.5, 89.5, 38.7, 36.9, 14.5. m/z (EI) 230 (100%,
M
+•), 123 (26).
2,2-Dioxo-7-methyl-4-piperidin-1-yl-2λ6-pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine 3b, 7-Methyl-3-piperidin-1-
yl-1,1,5-trioxo-1λ6-pyrazolo[1,2-b][1,2,3,5]thiatriazole 4b,
and 1,1-Dioxo-6-methyl-3-piperidin-1-yl-1λ6-pyrazolo
[3,2-b][1,4,3,5]oxathiadiazine 5b
Method A. Column chromatography (50–100% dichloro-
methane in light petroleum, then 0–5% ethyl acetate in
dichloromethane) gave three products.
3b (14% yield): Recrystallized from ethanol; colourless
crystals, mp 106–107◦C. (Found: C 44.6, H 5.2, N 20.9; M+•

Novel Pyrazolo-Fused Oxathiadiazines and Thiatriazoles
665
38.3, 36.6, 30.5, 21.5, 13.4. m/z (EI) 258 (8%, M+•), 243 (2),
230 (100).
CH2CH2CH3), 0.96 (3H, t, J 7.4, CH2CH2CH3). δC (75 MHz)
157.3, 151.0, 146.8, 92.5, 51.0, 48.5, 31.0, 26.1, 25.4, 23.9, 21.3,
13.7. m/z (EI) 298 (3%, M+•), 258 (3), 234 (68), 206 (22), 109
(86), 84 (100).
4-Diethylamino-2,2-dioxo-7-propyl-2λ6-pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine 3d, 3-Diethylamino-7-propyl-1,1,5-
trioxo-1λ6-pyrazolo[1,2-b][1,2,3,5]thiatriazole 4d, and
3-Diethylamino-6-propyl-1,1-dioxo-1λ6-pyrazolo[3,2-b]
[1,4,3,5]oxathiadiazine 5d
4e (2%yield): Obtained asan off-white powder, mp 65–67◦C.
(Found: M+• 298.1087. C12H18N4O3S requires M+•298.1094).
δH (300 MHz) 5.47 (1H, s, C=CH), 3.67 (2H, t, J 5.3, NCH2),
3.61 (2H, t, J 5.4, NCH2), 2.67 (2H, t, J 7.7, N=CCH2), 1.74
(6H, br s, 3 × CH2), 1.65–1.55 (2H, m, CH2CH2CH3), 1.03 (3H,
t, J 7.4, CH2CH2CH3). δC (75 MHz) 164.9, 163.9, 149.2, 105.0,
51.9, 48.7, 29.6, 25.9, 24.9, 23.4, 20.7, 13.5. m/z (EI) 298 (3%,
Method C. No precipitate after stirring vigorously overnight,
addition of diethyl ether (15 mL) and pH adjustment to 3. The
organic phase was washed with water, dried, and the solvent
was removed under reduced pressure to give a deep red, vis-
cous oil. Purification by column chromatography (50–100%
dichloromethane in light petroleum, then 0–5% ethyl acetate
in dichloromethane) afforded three products:
M
+•), 234 (52), 206 (18), 127 (13), 109 (81), 84 (100).
5e (13% yield): Recrystallized from isopropanol; colourless
crystals, mp 92–93◦C. (Found: C 48.4, H 6.2, N 18.9; M+•
298.1084. C12H18N4O3S requires C 48.3, H 6.1, N 18.8%;
M
+•298.1094). δH (300 MHz) 5.73 (1H, s, C=CH), 3.67 (4H,
3d (8% yield): Recrystallized from isopropanol; colourle+ss•
crystals, mp 59–60◦C. (Found: C 46.0, H 6.4, N 19.3; M
286.1087. C11H18N4O3S requires C 46.1, H 6.3, N 19.6%; M+•
286.1094). δH (400 MHz) 5.84 (1H, s, C=CH), 4.02 (2H, br q,
J 6.6, NCH2), 3.63 (2H, br q, J 6.6, NCH2), 2.58 (2H, t, J 7.5,
CH2CH2CH3), 1.69 (2H, tq, J 7.4, 7.4, CH2CH2CH3), 1.38 (3H,
br t, J 6.6, NCH2CH3), 1.33 (3H, br t, J 6.6, NCH2CH3), 0.98
(3H, t, J 7.4, CH2CH2CH3). δC (75 MHz) 157.2, 150.8, 147.1,
92.2, 46.4, 45.5, 30.9, 21.0, 13.7, 13.6, 11.8. m/z (EI) 286 (4%,
br s, CH2NCH2), 2.59 (2H, t, J 7.7, N=CCH2), 1.67 (6H, br s,
3 × CH2), 1.66–1.58 (2H, m, CH2CH2CH3), 0.93 (3H, t, J 7.5,
CH2CH2CH3). δC (75 MHz) 156.2, 148.1, 147.3, 88.4, 47.2,
45.8, 30.8, 25.4, 24.8, 23.4, 21.9, 13.6. m/z 298 (12%, M+•),
270 (100).
7,8-Dimethyl-4-dimethylamino-2,2-dioxo-2λ6-pyrazolo
[2,3-e][1,2,3,5]oxathiadiazine 3f, 5,6-Dimethyl-3-
dimethylamino-1,1-dioxo-1λ6-pyrazolo[3,2-b][1,4,3,5]
oxathiadiazine 5f, and 5,6-Dimethyl-3-dimethylamino-
1,1,7-trioxo-1λ6-pyrazolo[1,2-b][1,2,3,5]thiatriazole 6f
M
+•), 271 (5), 222 (38), 194 (29), 179 (30), 152 (21), 97 (100).
4d (2% yield): Colourless oil. (Found: C 46.1, H 6.5, N
19.8; M+• 286.1099. C11H18N4O3S requires C 46.1, H 6.3, N
19.6%; M+• 286.1094). δH (300 MHz) 5.48 (1H, s, C=CH),
3.70 (2H, q, J 7, NCH2), 3.55 (2H, q, J 7, NCH2), 2.68 (2H, t,
J 7.7, CH2CH2CH3), 1.75 (2H, tq, J 7.4, 7.4, CH2CH2CH3),
1.36–1.26 (6H, br m, 2 × NCH2CH3) 1.04 (3H, t, J 7.4,
CH2CH2CH3). δC (75 MHz) 164.7, 163.9, 149.9, 105.1, 46.7,
44.0, 29.6, 20.7, 13.5, 11.9. m/z (EI) 286 (5%, M+•), 271 (2),
222 (24), 207 (9), 194 (19), 179 (22), 97 (100), 72 (71).
MethodB. Columnchromatography(50–100%dichloromethane
in light petroleum) provided three compounds:
3f (7% yield): Recrystallized from isopropanol; colourless
crystals, mp 105–106◦C. (Found: C 39.4, H 5.0, N 23.2; M+•
244.0621. C8H12N4O3S requires C 39.3, H 5.0, N 22.9%; M+•
244.0625). δH (300 MHz) 3.62 (3H, br s, NCH3), 3.22 (3H, br
s, NCH3), 2.21 (3H, s, N=CCH3), 1.92 (3H, s, C=CCH3). δC
(75 MHz) 153.8, 148.0, 147.0, 101.3, 41.7, 40.2, 12.8, 5.7. m/z
(EI) 244 (64%, M+•), 180 (4), 137 (21), 125 (15), 124 (32),
54 (100).
5f (52% yield): Recrystallized from ethanol; colourless nee-
dles, mp 226.5–228.5◦C. (Found: C 39.4, H 5.0, N 22.9; M+•
244.0622. C8H12N4O3S requires C 39.3, H 5.0, N 22.9%; M+•
244.0625). δH (300 MHz) 3.23 (3H, s, NCH3), 3.19 (3H, s,
NCH3), 2.21 (3H, s, N=CCH3), 1.93 (3H, s, C=CCH3). δC
(75 MHz) 152.7, 149.9, 144.6, 97.5, 38.7, 36.7, 12.7, 6.0. m/z
(EI) 244 (100%, M+•), 137 (11).
5d (60% yield): Colourless oil. (Found: C 45.9, H 6.6, N 19.6;
M
M
+• 286.1087. C11H18N4O3S requires C 46.1, H 6.3, N 19.6%;
+• 286.1094). δH (400 MHz) 5.75 (1H, s, C=CH), 3.533 (2H,
q, J 7, NCH2), 3.526 (2H, q, J 7, NCH2), 2.59 (2H, t, J 7.5,
CH2CH2CH3), 1.64 (2H, tq, J 7.4, 7.4, CH2CH2CH3), 1.27
(3H, t, J 7, NCH2CH3), 1.25 (3H, t, J 7, NCH2CH3), 0.93 (3H,
t, J 7.4, CH2CH2CH3). δC (75 MHz) 155.9, 148.8, 147.2, 88.4,
44.5, 42.9, 30.6, 21.6, 13.4, 13.3, 11.9. m/z (EI) 286 (10%, M+•),
258 (100).
2,2-Dioxo-4-piperidin-1-yl-7-propyl-2λ6-pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine 3e, 3-Piperidin-1-yl-7-propyl-1,1,5-
trioxo-1λ6-pyrazolo[1,2-b][1,2,3,5]thiatriazole 4e, and
1,1-Dioxo-6-propyl-3-piperidin-1-yl-1λ6-pyrazolo[3,2-b]
[1,4,3,5]oxathiadiazine 5e
6f (11% yield): Obtained as an off-white powder, mp
210–211◦C. (Found: C 39.5, H 5.0, N 22.6; M+• 244.0622.
C8H12N4O3S requires C 39.3, H 5.0, N 22.9%; M+• 244.0625).
δH (300 MHz) 3.13 (6H, s, 2 × NCH3), 2.32 (3H, s, N=CCH3),
1.79 (3H, s, C=CCH3). NOE observed between δ 3.13 and δ
2.32. δC (75 MHz) 154.5, 152.3, 149.6, 88.8, 41.5, 13.5, 7.2. m/z
(EI) 244 (53%, M+•), 137 (10), 54 (100).
Method B. No effective precipitation on dilution with water.
The mixture was extracted with dichloromethane (10 mL).
The organic phase was washed with water and the solvent
was removed under reduced pressure affording a viscous
red oil. Purification by column chromatography (50–100%
dichloromethane in light petroleum followed by 0–5% ethyl
acetate in dichloromethane) provided three products:
7,8-Dimethyl-4-diethylamino-2,2-dioxo-2λ6-pyrazolo
[2,3-e][1,2,3,5]oxathiadiazine 3g and 5,6-Dimethyl-3-
diethylamino-1,1-dioxo-1λ6-pyrazolo[3,2-b][1,4,3,5]
oxathiadiazine 5g
3e (2% yield): Recrystallized from isopropanol; colourless
prisms, mp 80–82◦C. (Found: C 48.4, H 6.1, N 19.0, S 10.8;
M+• 298.1088. C12H18N4O3S requires C 48.3, H 6.1, N 18.8,
S 10.8%; M+• 298.1094). δH (300 MHz) 5.85 (1H, s, C=CH),
4.32 (2H, br s, NCH2), 3.77 (2H, br s, NCH2), 2.58 (2H, t, J 7.7,
N=CCH2), 1.75 (6H, br s, 3 × CH2), 1.68 (2H, tq, J 7.5, 7.5,
MethodA. Columnchromatography(50–100%dichloromethane
in light petroleum, then 0–5% ethyl acetate in dichloromethane)
afforded two products:
3g (13% yield): Recrystallized from isopropanol; colourle+ss•
crystals, mp 91–92◦C. (Found: C 44.2, H 6.1, N 20.8; M
272.0934. C10H16N4O3S requires C 44.1, H 5.9, N 20.6%; M+•

666
C. M. Forsyth et al.
272.0938). δH (300 MHz) 4.00 (2H, br q, J 6, NCH2), 3.59
(2H, br q, J 5.7, NCH2), 2.20 (3H, s, N=CCH3), 1.92 (3H, s,
C=CCH3), 1.32 (6H, br s, N(CH2CH3)2). δC (75 MHz) 153.8,
147.1, 147.0, 101.1, 46.1, 45.4, 13.7, 12.9, 11.9, 5.8. m/z (EI)
272 (37%, M+•), 208 (57), 180 (21), 165 (48), 139 (16), 138
(41), 137 (32), 97 (90), 72 (100).
5g (26% yield): Recrystallized from isopropanol; colourle+ss•
crystals, mp 167–168◦C. (Found: C 44.4, H 6.0, N 20.5; M
272.0936. C10H16N4O3S requires C 44.1, H 5.9, N 20.6%; M+•
272.0938). δH (300 MHz) 3.54 (4H, q, J 7.2, CH2NCH2), 2.22
(3H, s, N=CCH3), 1.91 (3H, s, C=CCH3), 1.29 (3H, t, J 6.5,
NCH2CH3), 1.25 (3H, t, J 6.5, NCH2CH3). δC (75 MHz) 152.7,
148.9, 144.3, 97.2, 44.4, 42.9, 13.3, 12.4, 11.9, 5.7. m/z (EI)
272 (72%, M+•), 165 (5), 152 (11), 151 (16), 98 (22), 83 (34),
54 (100).
(EI) 270 (71%, M+•), 177 (9), 163 (8), 150 (25), 110 (31), 108
(56), 80 (52), 79 (100).
Method C resulted in isolation of only 5h in 40% yield.
4-Diethylamino-2,2-dioxo-7,8,9,10-tetrahydro-2λ6-
[1,2,3,5]oxathiadiazino[5,6-b]indazole 3i, 3-Diethylamino-
1,1-dioxo-5,6,7,8-tetrahydro-1λ6-[1,4,3,5]oxathiadiazino
[3,2-b]indazole 5i, and 3-Diethylamino-5,6,7,8-tetrahydro-
1,1,9-trioxo-1λ6-[1,2,3,5]thiatriazolo[3,2-a]indazole 6i
Method B. Column chromatography (dichloromethane) afforded
three isomers:
3i (2% yield): Recrystallized from isopropanol; colourle+ss•
crystals, mp 128–130◦C. (Found: C 48.4, H 6.1, N 18.8; M
298.1086. C12H18N4O3S requires C 48.3, H 6.1, N 18.8%; M+•
298.1094). δH (300 MHz) 4.02 (2H, br s, NCH2), 3.63 (2H, br s,
NCH2), 2.64 (2H, t, J 6, CH2C=C), 2.50 (2H, t, J 6, N=CCH2),
1.82–1.74 (4H, m, 2 × CH2), 1.33 (6H, br s, 2 × NCH2CH3).
δC (75 MHz) 155.1, 152.5, 147.3, 102.5, 46.2, 45.5, 24.1, 22.5,
22.1, 18.3, 13.9, 12.1. m/z (EI) 298 (24%, M+•), 234 (36), 191
(46), 164 (43), 163 (27), 138 (46), 97 (60), 79 (64), 72 (100).
5i (37% yield): Recrystallized from acetonitrile; small,
colourless needles, mp 178–180◦C. (Found: C 48.4, H 6.2, N
19.0; M+• 298.1086. C12H18N4O3S requires C 48.3, H 6.1, N
18.8%; M+• 298.1094). δH (400 MHz) 3.57 (2H, q, J 7, NCH2),
3.53 (2H, q, J 7, NCH2), 2.72 (2H, t, J 6.2, CH2C=C), 2.47 (2H,
t, J 6.2, N=CCH2), 1.86–1.70 (4H, m, 2 × CH2), 1.31 (3H, t, J 7,
NCH2CH3), 1.29 (3H, t, J 7, NCH2CH3). δC (100 MHz) 153.8,
149.2, 143.2, 99.0, 44.7, 43.0, 23.9, 22.6, 22.1, 18.4, 13.6, 12.2.
m/z (EI) 298 (100%, M+•), 178 (30), 177 (52), 163 (22), 108
(79), 80 (59), 79 (82).
4-Dimethylamino-2,2-dioxo-7,8,9,10-tetrahydro-2λ6-
[1,2,3,5]oxathiadiazino[5,6-b]indazole 3h,
3-Dimethylamino-6,7,8,9-tetrahydro-1,1,5-trioxo-1λ6-
[1,2,3,5]thiatriazolo[2,3-a]indazole 4h, 3-Dimethylamino-
1,1-dioxo-5,6,7,8-tetrahydro-1λ6-[1,4,3,5]oxathiadiazino
[3,2-b]indazole 5h, and 3-Dimethylamino-5,6,7,8-
tetrahydro-1,1,9-trioxo-1λ6-[1,2,3,5]triatriazolo
[3,2-a]indazole 6h
MethodA. Columnchromatography(50–100%dichloromethane
in light petroleum, then 0–5% ethyl acetate in dichloromethane)
provided four products:
3h (17% yield): Recrystallized from isopropanol; colour-
less crystals, mp 134–135◦C. (Found: C 44.6, H 5.4, N 21.0;
M
+• 270.0779. C10H14N4O3S requires C 44.4, H 5.2, N 20.7%;
6i (17% yield): Recrystallized from acetonitrile; colourle+ss•
needles, mp 229–231◦C. (Found: C 48.4, H 6.2, N 19.0; M
298.1090. C12H18N4O3S requires C 48.3, H 6.1, N 18.8%; M+•
298.1094). δH (500 MHz) 3.51 (4H, q, J 7.2, NCH2), 2.58 (2H,
tt, J 6.1, 1.9, CH2C=C), 2.31 (2H, t, J 6.1, 1.9, N=CCH2),
1.90–1.83 (2H, m, CH2), 1.76–1.69 (2H, m, CH2), 1.28 (6H, t,
J 7.2, NCH2CH3). NOE observed between δ 3.51 and δ 2.58.
δC (50 MHz) 167.2, 157.9, 153.3, 115.9, 44.8, 25.1, 21.8, 20.6,
18.9, 12.4. m/z (EI) 298 (88%, M+•), 178 (25), 177 (45), 163
(22), 108 (72), 80 (65), 79 (100).
M+• 270.0781). δH (300 MHz) 3.60 (3H, br s, NCH3), 3.21
(3H, br s, NCH3), 2.61 (2H, t, J 5.9, C=CCH2), 2.45 (2H, t,
J 5.9, N=CCH2), 1.79–1.72 (4H, m, 2 × CH2). δC (75 MHz)
154.9, 148.0, 145.5, 102.4, 41.8, 40.1, 23.8, 22.2, 21.8, 18.0.
m/z (EI) 270 (98%, M+•), 163 (37), 151 (26), 150 (59), 108 (22),
79 (100).
4h (6% yield): Recrystallized from isopropanol; large,
colourless prisms, mp 148–150◦C. (Found: C 44.6, H 5.3, N
20.9; M+• 270.0781. C10H14N4O3S requires C 44.4, H 5.2, N
20.7%; M+• 270.0781). δH (300 MHz) 3.30 (3H, s, NCH3), 3.14
(3H, s, NCH3), 2.63 (2H, t, J 5.2, CH2C=C), 2.25 (2H, t, J 5.2,
N=CCH2), 1.86–1.83 (2H, m, CH2), 1.75–1.72 (2H, m, CH2).
δC (100 MHz) 164.9, 158.7, 151.4, 116.4, 41.9, 39.5, 22.9, 21.05,
21.04, 19.0. m/z (EI) 270 (100%, M+•), 163 (36), 151 (26), 150
(57), 80 (44), 79 (96).
4-Diethylamino-2,2-dioxo-7-phenyl-2λ6-pyrazolo
[2,3-e][1,2,3,5]oxathiadiazine 3j and 3-Diethylamino-
1,1-dioxo-6-phenyl-1λ6-pyrazolo[3,2-b][1,4,3,5]
oxathiadiazine 5j
5h (23% yield): Recrystallized from dichloromethane/ethyl
acetate; colourless, flat needles, mp 227–229◦C. (Found: C 44.5,
H 5.3, N 20.9, S 11.9; M+• 270.0779. C10H14N4O3S requires C
44.4, H5.2, N20.7, S11.9%;M+• 270.0781). δH (400 MHz)3.22
(3H, s, NCH3), 3.21 (3H, s, NCH3), 2.72 (2H, t, J 6.3, CH2C=C),
2.47 (2H, t, J 6.3, N=CCH2), 1.86–1.78 (2H, m, CH2), 1.78–
1.71 (2H, m, CH2). δC (125 MHz) 154.0, 149.9, 143.1, 99.1,
38.8, 36.8, 23.9, 22.6, 22.2, 18.5. m/z (EI) 270 (100%, M+•),
177 (8), 163 (6), 150 (22), 108 (51), 80 (34), 79 (67).
6h (17% yield): Recrystallized from dichloromethane/
acetonitrile (1:2); colourless needles, mp 248–249◦C. (Found:
C 44.4, H 5.3, N 20.9; M+• 270.0783. C10H14N4O3S requires
C 44.4, H 5.2, N 20.7%; M+• 270.0781). δH (500 MHz) 3.13
(6H, s, NMe2), 2.60 (2H, tt, J 6.1, 1.9, CH2C=C), 2.32 (2H, tt, J
6.2, 1.9, C=CCH2), 1.91–1.83 (2H, m, CH2), 1.77–1.69 (2H, m,
CH2). NOE observed between δ 3.13 and δ 2.60. δC (125 MHz)
167.0, 157.8, 154.0, 116.2, 41.2 (2C), 25.2, 21.8, 20.6, 19.0. m/z
Method B. Column chromatography (dichloromethane) pro-
vided two products: 3j (1% yield) and 5j (47% yield).
Method C. Column chromatography (50–100% dichloro-
methane in light petroleum) afforded two products: 3j (1% yield)
and 5j (58% yield).
3j: Recrystallized from ethanol; colourless crystals, mp
181–183◦C. (Found: C 52.6, H 5.1, N 17.6; M+• 320.0936.
C14H16N4O3S requires C 52.5, H 5.0, N 17.5%; M+• 320.0938).
δH (300 MHz) 7.80–7.77 (2H, m,ArH), 7.47–7.45 (3H, m,ArH),
6.36 (1H, s, C=CH), 4.10 (2H, q, J 7, NCH2), 3.68 (2H, q, J
7, NCH2), 1.52 (3H, t, J 6.8, NCH2CH3), 1.37 (3H, t, J 6.9,
NCH2CH3). δC (75 MHz) 154.1, 151.6, 147.2, 130.7, 130.1,
128.9, 126.2, 90.6, 46.6, 45.8, 13.9, 11.9. m/z (EI) 320 (5%,
M
+•), 256 (39), 160 (39), 103 (11), 102 (100).
5j: Recrystallized from isopropanol; large, colourle+ss•
rhombs, mp 191–192◦C. (Found: C 52.4, H 5.0, N 17.7; M
320.0935. C14H16N4O3S requires C 52.5, H 5.0, N 17.5%; M+•

Novel Pyrazolo-Fused Oxathiadiazines and Thiatriazoles
667
Table 2a. Crystal data and structure refinement for 3f, 3h, 3i, 4b, 4h, and 5f
3f
3h
3i
4b
4h
5f
CCDC no.
Empirical formula
Formula weight
Crystal system
Space group
Unit cell dimensions
a [Å]
752406
C8H12N4O3S
244.28
Monoclinic
P21/c
752405
C10H14N4O3S
270.31
Monoclinic
P21/c
752408
C12H18N4O3S
298.36
Orthorhombic
Pbca
752411
C10H14N4O3S
270.31
Monoclinic
P21/c
752414
C10H14N4O3S
270.31
Orthorhombic
Pbca
752407
C8H12N4O3S
244.28
Triclinic
P1
11.7385(2)
11.6488(2)
8.5485(1)
90
109.752(1)
90
1100.14(3)
4
1.475
10.8594(3)
10.8458(2)
10.1386(1)
90
91.765(1)
90
1193.55(4)
4
1.504
10.1488(1)
11.4196(1)
23.8679(4)
90
90
90
2766.18(6)
8
1.433
8.7518(1)
11.1197(2)
11.9908(2)
90
91.570(1)
90
1166.48(3)
4
1.539
11.3202(2)
13.2699(2)
15.3511(3)
90
90
90
2306.01(4)
8
1.557
7.9492(8)
8.6774(11)
8.7656(11)
85.978(6)
74.283(7)
66.742(6)
534.27(11)
2
b [Å]
c [Å]
α [◦]
β [◦]
γ [◦]
Volume [Å3]
Z
ρ (calc.) [mg m−3
]
1.518
0.302
µ [mm−1
]
0.294
0.279
0.248
0.285
0.289
Crystal size [mm]
θ range [◦]
Ntotal
0.25 × 0.25 × 0.25 0.25 × 0.13 × 0.13 0.25 × 0.13 × 0.10 0.25 × 0.25 × 0.25 0.30 × 0.25 × 0.2005 0.25 × 0.25 × 0.25
1.84 to 27.49
10921
1.88 to 27.49
12411
1.71 to 27.50
27230
2.33 to 27.50
12001
2.65 to 27.50
21682
2.42 to 25.00
4594
N (Rint
Nobs [I > 2σ(I)]
)
2487 (0.045)
2007
2739 (0.055)
1810
3177 (0.50)
2418
2676 (0.037)
2107
2651 (0.053)
1999
1816 (0.055)
1505
R indices [I > 2σ(I)]
R1
wR2
0.0408
0.1047
0.0458
0.0961
0.0407
0.0985
0.0432
0.1045
0.0433
0.1098
0.0506
0.1392
R indices (all data)
R1
wR2
GoF (on F2)
0.0537
0.1128
1.059
0.0866
0.1107
1.057
0.0605
0.1116
1.032
0.0602
0.1152
1.067
0.0646
0.1231
1.046
0.0610
0.1494
1.107
Table 2b. Crystal data and structure refinement for 5h, 5i, 5j, 5k, and 6i
5h
5i
5j
5k
6i
CCDC no.
Empirical formula
Formula weight
Crystal system
Space group
Unit cell dimensions
a [Å]
752413
752409
C12H18N4O3S
298.36
Orthorhombic
P212121
752410
C14H16N4O3S
320.37
Monoclinic
P21/n
752412
C15H16N4O3S
332.38
Orthorhombic
Pbca
752415
C12H18N4O3S
298.36
Triclinic
P1
C
10H14N4O3S
270.31
Monoclinic
P21/c
7.4680(2)
12.2561(4)
13.2592(5)
90
101.085
90
1190.95(7)
4
1.508
8.7345(2)
9.2597 (2)
17.2306(3)
90
90
90
1393.59(5)
4
1.422
9.1977(1)
11.1893(2)
14.6360(2)
90
106.409(1)
90
1444.92(4)
4
1.473
11.5588(2)
14.9942(2)
17.1453(3)
90
90
90
2971.54(8)
8
1.486
8.313(2)
8.7490(11)
9.972(2)
76.606(10)
75.215(10)
88.831(10)
681.6(2)
2
b [Å]
c [Å]
α [◦]
β [◦]
γ [◦]
Volume [Å3]
Z
ρ (calc.) [mg m−3
]
1.454
0.252
µ [mm−1
]
0.279
0.246
0.243
0.240
Crystal size [mm]
θ range [◦]
Ntotal
0.30 × 0.10 × 0.10
2.28 to 27.50
14809
0.25 × 0.10 × 0.10
2.36 to 27.50
13694
0.25 × 0.25 × 0.25
2.33 to 27.50
17656
0.25 × 0.25 × 0.10
2.52 to 27.50
30620
0.15 × 0.10 × 0.05
2.17 to 27.50
4783
N (Rint
Nobs [I > 2σ(I)]
)
2730 (0.057)
2244
3193 (0.055)
2406
3277 (0.056)
2603
3402 (0.059)
2480
2328 (0.043)
1720
R indices [I > 2σ(I)]
R1
wR2
0.0432
0.0940
0.0449
0.0972
0.0440
0.1062
0.0463
0.1166
0.0643
0.1145
R indices (all data)
R1
wR2
xabs
GoF (on F2)
0.0605
0.0999
0.0744
0.1099
−0.04(10)
1.051
0.0608
0.1182
0.0729
0.1332
0.0953
0.1252
1.053
1.038
1.059
1.070

668
C. M. Forsyth et al.
320.0938). δH (300 MHz) 7.87–7.83 (2H, m, ArH), 7.46–7.38
(3H, m, ArH), 6.24 (1H, s, C=CH), 3.59 (2H, q, J 7, NCH2),
3.57 (2H, q, J 7, NCH2), 1.33 (3H, t, J 7, NCH2CH3), 1.31 (3H, t,
J 7, NCH2CH3). δC (75 MHz) 153.1, 148.9, 147.8, 131.2, 129.5,
128.7, 126.2, 86.8, 44.8, 43.1, 13.7, 12.2. m/z (EI) 320 (48%,
References
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+•), 272 (4), 199 (10), 103 (11), 102 (100).
2,2-Dioxo-7-phenyl-4-piperidin-1-yl-2λ6-pyrazolo[2,3-e]
[1,2,3,5]oxathiadiazine 3k and 1,1-Dioxo-6-phenyl-
3-piperidin-1-yl-1λ6-pyrazolo[3,2-b][1,4,3,5]
oxathiadiazine 5k
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Method D. Column chromatography (dichloromethane/light
petroleum, 1:1) provided two products:
3k (2% yield): Recrystallized from isopropanol; colourle+ss•
crystals, mp 189–191◦C. (Found: C 54.1, H 4.9, N 16.7; M
332.0933. C15H16N4O3S requires C 54.2, H 4.9, N 16.9%; M+•
332.0938). δH (300 MHz) 7.80–7.77 (2H, m, ArH), 7.47–7.45
(3H, m, ArH), 6.37 (1H, s, C=CH), 4.41 (2H, br s, NCH2), 3.83
(2H, br s, NCH2), 1.82 (6H, br s, 3 × CH2). δC (75 MHz) 154.3,
151.8, 147.1, 130.9, 130.5, 129.2, 126.5, 91.2, 51.5, 49.1, 26.5,
25.8, 24.2. m/z (EI) 332 (3%, M+•), 269 (12), 268 (75), 161 (11),
160 (52), 109 (48), 102 (100), 84 (68).
5k (16% yield): Recrystallized from ethanol; colourle+ss•
crystals, mp 254–256◦C. (Found: C 54.4, H 4.9, N 16.8; M
332.0936. C15H16N4O3S requires C 54.2, H 4.9, N 16.9%; M+•
332.0938). δH (300 MHz) 7.86–7.84 (2H, m, ArH), 7.43–7.41
(3H, m, ArH), 6.23 (1H, s, C=CH), 3.73 (4H, br s, 2 × NCH2),
1.73 (6H, br s, 3 × CH2). δC (75 MHz) 153.2, 148.0, 147.7,
131.2, 129.5, 128.7, 126.2, 86.8, 47.5, 46.0, 25.6, 24.9, 23.5. m/z
(EI) 332 (48%, M+•), 239 (11), 110 (9), 103 (11), 102 (100).
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X-Ray Crystallography
Single crystals suitable for X-ray analysis were covered in vis-
cous oil and mounted on a glass fibre. Data (2θmax 50–55◦)
were collected at 123(1) K using either a Nonius KAPPA or
Bruker X8 Apex CCD diffractometer and MoKα (λ 0.71073 Å)
radiation. After integration and scaling, datasets (Ntotal) were
merged to N unique reflections (Rint as quoted) with Nobs con-
sidered ‘observed’ with I > 2σ(I). The structures were solved
using conventional methods and refined by full matrix least-
squares using the SHELX-97 software,[27] in conjunction with
the X-Seed interface.[28] Non-hydrogen atoms were refined
with anisotropic thermal parameters and hydrogen atoms were
placed in calculated positions. Molecular diagrams (Figs 1–4)
are shown with 50% thermal ellipsoids and hydrogen atoms
as spheres of arbitrary size. Data were corrected for absorp-
tion using either SORTAV[29a] or SADABS.[29b] For struc-
ture 5i, the Flack parameter xabs was refined (see Table 2).
CCDC 752405–752415 contain the supplementary crystallo-
graphic 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.
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BF00507082
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[28] L. J. Barbour, J. Supramol. Chem. 2001, 1, 189. doi:10.1016/
S1472-7862(02)00030-8
[29] (a) R. H. Blessing, J. Appl. Cryst. 1997, 30, 421. doi:10.1107/
S0021889896014628
Acknowledgements
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.
(b) G. M. Sheldrick, SADABS: Program for Scaling and Absorp-
tion Correction of Area Detector Data 1997 (Universität Göttingen:
Göttingen).