N,N -Dialkyl- N′ -Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. Part XV.

Article abstract of DOI:10.1071/CH18252

N,N-Dimethyl-N′-chlorosulfonyl chloroformamidine 1a underwent reactions with various anilines. In addition to the benzo[e][1,2,4]thiadiazine dioxides 8, from 1,3-NCC bis-nucleophilic substitution and bis-anilino adducts 9, some unexpected products were fo

Full text of DOI:10.1071/CH18252

CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
https://doi.org/10.1071/CH18252
N,N-Dialkyl-N9-Chlorosulfonyl Chloroformamidines
in Heterocyclic Synthesis. Part XV.* Some Unexpected
Reactions with Anilines
A
A
B
Dylan Innes, Michael V. Perkins, Andris J. Liepa, and
B C
,
Craig L. Francis
A
College of Science and Engineering, Flinders University, Bedford Park, SA 5042,
Australia.
B
Biomedical Synthetic Chemistry Group, CSIRO, Clayton, Vic. 3168, Australia.
C
Corresponding author. Email: craig.francis@csiro.au
N,N-Dimethyl-N0-chlorosulfonyl chloroformamidine 1a underwent reactions with various anilines. In addition to the
benzo[e][1,2,4]thiadiazine dioxides 8, from 1,3-NCC bis-nucleophilic substitution and bis-anilino adducts 9, some
unexpected products were formed, particularly when sterically hindered or electron-poor anilines were used. In these
cases, products such as the [1,3,2,4,6]dithiatriazine 1,1,3,3-tetraoxides 17 and, on occasion, N,N,5-trimethyl-4-(aryli-
mino)-4,5-dihydro-[1,3,5]triazin-2-amines 14 were produced in significant yields. Reaction of dichloride 1a with
3-bromoaniline afforded the unusual eight-membered-ring product 2,6-bis(3-bromophenyl)-3,7-bis(dimethylamino)-
2H,6H-[1,5,2,4,6,8]dithiatetrazocine 1,1,5,5-tetraoxide 28, in addition to the dithiatriazine tetraoxide 17k. These
uncommon heterocyclic structures are of interest for bioactive molecule discovery screening programs.
Manuscript received: 28 May 2018.
Manuscript accepted: 8 August 2018.
Published online: 12 September 2018.
Introduction
In each case, the exocyclic nucleophile reacted at the
amidinyl carbon atom of dichloride 1 and the ring nucleophile
reacted at the sulfamoyl moiety. In this context, we noted that in
the initial study of dichlorides 1 by Markovskii et al., the product
of the reaction of aniline 6a with dichloride 1a was assigned the
structure 7a rather than the isomeric structure 8a (Scheme 2),[4]
which is inconsistent with our later and more detailed studies of
these systems.
As part of our ongoing research program studying the generation
of novel heterocyclic ring systems from N,N-dialkyl-N0-chlor-
osulfonyl chloroformamidines 1,[1] recent efforts have focussed
on reactions with 1,3-NCC bis-nucleophiles. Previous reports
detailed the regioselective reactions of 1 with 1-substituted-5-
aminopyrazoles 2[2] and 1H-benzimidazol-2-ylacetonitriles 3
(and related compounds)[3] to afford new pyrazolo[3,4-e][1,2,4]
thiadiazine dioxides 4[2] and benzo[4,5]imidazo[1,2-b][1,2,6]
thiadiazine dioxides 5[3] respectively (Scheme 1).
In light of our recent results,[2,3] we considered it likely that
the incorrect structure may have been assigned, so we revisited
O
exocyclic NuN
ring NuC
R1
O
ring NuN
H
N
N
S
N
R2N
R3
R3
NR2
CN
exocyclic NuC
N
R2
N
H
N
R3
R3
N
N
H
S
N
R2
H2N
R2N
O
N
R1
O
5
N
2
Cl
Cl
CN
4
3
N
O
R2
S
R2N
N
N
N
O
1
O
O
R3
R3
R1
S
R2N
N
N
H
CN
N
NH
S
O
O
Scheme 1.
*Part XIV, Aust. J. Chem. 2018, 71, 58.
Journal compilation ꢀ CSIRO 2018
www.publish.csiro.au/journals/ajc

B
D. Innes et al.
Me2N
H
N
H
N
O
NMe2
NH2
Cl
Cl
Et3N
S
N
ꢀ
O
N
O
N
S
S
6a
O
O
O
NMe2
1a
7a
8a
Scheme 2.
exocyclic NuC
NC
reacted with the bis-adduct to provide a stabilised leaving group
for elimination to a sulfonylguanidine intermediate, facilitating
attack by the ortho carbon of the phenyl group at the sulfony-
limino moiety (Scheme 4).
exocyclic NuN
NH2
The reaction between the dichloride 1a and N-methylaniline
10 was examined to determine the effect of N-substitution on the
formation of the benzothiadiazine ring system (Scheme 5). Only
the bis-adduct 11 was isolated, indicating that the addition of the
methyl substituent prevented the formation of the sulfonylgua-
nidine intermediate by blocking elimination of HCl, leaving the
sulfamoyl chloride moiety open to further attack by another
equivalent of N-methylaniline.
2-(2-Aminophenyl)acetonitrile 6b has potential 1,3-NCC
bis-nucleophilicity similar to other aniline derivatives, but it
also has potential reactivity at the exocyclic CH2 moiety, which
is activated by the adjacent nitrile group. Therefore, it was
envisaged that 6b may react with the dichloride 1a to give the
benzothiadiazine dioxide 8c and/or the seven-membered ring
product(s) 12 and/or 13 (Scheme 6).
The treatment of compound 6b with the dichloride 1a at
808C in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone
(dimethylpropylene urea, DMPU) (Method B), followed by
dilution of the reaction mixture with water and extraction with
either ethyl acetate or dichloromethane did not provide any
identifiable products. However, basification and extraction with
ethyl acetate followed by chromatographic purification
ring NuC
6b
Fig. 1. Potentially nucleophilic sites of 2-(2-aminophenyl)acetonitrile 6b.
this chemistry with the aim of unambiguously confirming the
regioselectivity of the reactions of dichlorides 1 with a range of
anilines.
Additionally, given the regioselectivity of the reactions
of dichlorides 1 with 1H-benzimidazol-2-ylacetonitriles 3
(Scheme 1),[3] we were also particularly interested in exploring
the relative nucleophilicities of the three potentially nucleo-
philic sites available in the substituted aniline derivative 2-(2-
aminophenyl)acetonitrile 6b (Fig. 1).
Results and Discussion
The reaction of dichloride 1a[1] with 4-ethylaniline 6c in CH2Cl2
in the presence of Et3N at room temperature (rt) overnight
(Method A) gave the anticipated benzothiadiazine 8b
(Scheme 3), the structure of which was confirmed by X-ray
crystallography (Fig. 2). The bis-adduct 9b was also isolated,
presumably due to the higher reactivity of the exocyclic NH2
group compared with the ortho carbon nucleophile of the ring.
The X-ray crystallographic examination of structure 8b
confirmed that the exocyclic amino group of the aniline 6c
reacted at the amidinyl carbon atom of dichloride 1a and the ring
nucleophile reacted at the sulfamoyl moiety. Furthermore, this
result also revealed that the earlier assignment of benzo[c]
[1,2,6]thiadiazine 2,2-dioxide structure 7a[4] (Scheme 2) was
incorrect, and in fact the correct structure was the isomeric
benzo[e][1,2,4]thiadiazine 1,1-dioxide 8a.
Treatment of bis-adduct 9b with the dichloride 1a in the
presence of Et3N resulted in a complex mixture, which gave 8b
as the only identifiable product (Scheme 3). No reaction
occurred in the absence of the dichloride, suggesting that 1a
Fig. 2. ORTEP diagram of 8b.
H
N
H
N
NMe2
NMe2
NH2
1a
Et3N, CH2Cl2
ꢀ
Et
N
N
S
Et
Et
rt, 6 h
Et
O
S
8b
O
O
N
H
6c
O
9b
(32 %)
(29 %)
1a, Et3N, ClCH2CH2Cl
50ꢁC
(19 %)
Scheme 3.

N,N-Dialkyl-N0-Chlorosulfonyl Chloroformamidines. XV
C
H
N
H
N
Cl
N
H
NMe2
S
NMe2
N
O
O
Et
NMe2
Et
N
Et
N
Et
ꢀ
Et
O
S
O
S
N
9b
N
H
O
O
NMe2
N
N
NMe2
NMe2
N
Cl
S
O
Et
Cl
S
O
O
N
O
Cl
O
S
1a
O
8b
Scheme 4.
NMe2
N
NMe2
H
N
Cl
1a
Me
N
S
Me
ꢀ
N
Me
Et3N, CH2Cl2
rt, 3 days
N
O
Cl
S
O
O
O
10
1a
11 (48 %)
Scheme 5.
exocyclic NuC
NC
exocyclic NuN
NC
O
H
N
NMe2
H
H
O
N
NMe2
N
NH2
S
1a
N
N
N
S
S
O
ring NuC
NMe2
O
O
O
NC
NC
6b
8c
13
12
Scheme 6.
NC
NC
Me
N
1a
NMe2
NH
N
O
NH2
N
1. DMPU, 80ꢁC, 16 h
ꢀ
N
N
2. NaOH
NMe2
6b
15 (5 %)
14c (12 %)
Scheme 7.
provided the unexpected and previously unreported triazine 14c
as well as the known quinazolinone 15[5] (Scheme 7). The
anticipated benzothiadiazine or seven-membered ring products
were not observed.
X-ray crystallography confirmed the structures of these
products (Fig. 3 and Supplementary Material).
Conducting the reaction of 6b and 1a in CH2Cl2 in the
presence of Et3N (Method A) provided a black tarry solid after
dilution with water and extraction with ethyl acetate. Adjust-
ment of the aqueous phase to pH 10 with NaOH precipitated the
triazine 14c (13 %) as a tan solid.
A proposed mechanism for the formation of products 14c
and 15 is presented in Scheme 8. Initially, the amino group of 6b
could react at the amidinyl carbon of the dichloride 1a to form
intermediate A. The guanidine nitrogen of A could react with a
second equivalent of the dichloride to give B (shown with blue
Fig. 3. ORTEP diagram of 14c.

D
D. Innes et al.
ꢂ
N
N
OH
ꢀ
N
H
H
H
N
H
ꢂ
ꢀ
SO2-Cl
N
N
H
N
N
H
N
OH
ꢀ
N
-Me2NCN
N
N
N
N
N
SO2Cl
-SO2
-HCl
ꢂ
SO2-Cl
N
Cl
N
N
N
H
SO2Cl
CN
G
ClO2S
A
Cl-O2S
F
N
B
OH
N
ClO2S
-SO2
-HCl
-SO2
-2HCl
N
OHꢂ
N
N
H
N
ꢀ
H
N
N
H
N
N
ꢀ
N
N
N
N
N
N
SO2Cl
SO2Cl
CN
ꢂ
OH
D
N
C
H
ꢀ
N
N
OH-
H
H
N
H
N
N
N
N
N
N
N
N
N
N
N
-HCN
-SO2
-HCl
N
N
N
CN
H
O
SO2-Cl
O
15
I
E
N
14c
OH
Scheme 8.
O
N
S
NMe2
O
ꢂ
Bn
ꢀ
Et3N
Bn
N
N
H
H
N
H
S
N
S
O
O
NMe2
NH2
N
O
O
18
16
19
Fig. 4. Structures of side products 16, 18, and 19.
arrows), which under basic conditions may eliminate SO2 and
HCl to give the terminal iminium cation C. This could undergo
an intramolecular iminium cyclisation followed by loss of SO2
and HCl to give the final triazine product 14c. The quinazoli-
none 15 could be formed by the pathway indicated by red
arrows in Scheme 8. Deprotonation of the activated methylene
group of B followed by attack of the resulting carbanion on the
bis-sulfonyl guanidine moiety would afford the iminoquinazo-
line intermediate G. Oxidation via deprotonation of the
activated benzylic methane group of G and loss of SO2 would
lead to intermediate H. Nucleophilic attack of hydroxide ion
on H as shown would provide a quinazoline cyanohydrin
I. Elimination of HCN from I would afford the observed
quinazolinone 15.[5]
The above results suggested that the CH2CN moiety of 6b did
not possess sufficient nucleophilicity to react with dichloride 1a;
however, the remarkable and unexpected production of the
triazine 14c prompted us to investigate further the reactions of
dichloride 1a with variously substituted anilines, initially with
an emphasis on ortho-substituted compounds, which we antici-
pated might favour the formation of triazines 14.
but also afforded a significant amount of the guanidine 19
(Scheme 9, Table 1). Compound 19 presumably forms via
hydrolysis of the analogue of intermediate A in Scheme 8. On
one occasion when carrying out this reaction, an additional
product, the sulfamide 16 (Fig. 4), was isolated in ,10 % yield.
The formation of sulfamide 16 was traced back to an impure
batch of dichloride 1a, presumably contaminated with sulfuryl
chloride, which reacted with the aniline 6d. Formation of
sulfamides from reactions of amines with sulfuryl chloride has
been reported previously.[6,7]
Treatment of2-benzylaniline 6dwith dichloride 1aindichlor-
omethane solution in the presence of triethylamine afforded the
expected benzothiadiazine 8d, in 14 % yield, but the major
product was the unexpected [1,3,2,4,6]dithiatriazine tetraoxide
17d, isolated in 66% yield (Scheme 9, Table 1). Interestingly, the
triethylammonium [1,3,2,4,6]dithiatriazin-2-ide salt 18 (Figs 4
and 5) was also isolated in low yield. Basification of the aqueous
phase with NaOH and extraction providedthe triazine14d, which
was isolated as the crystalline hydrobromide salt. The structures
of 14d, 18, and analogues of 17d (see below) were confirmed by
X-ray crystallographic analysis.
Heating a mixture of 2-benzylaniline 6d and dichloride 1a
in DMPU at 808C gave a low yield of the benzothiadiazine 8d,
Treatment of 2-phenylaniline 6e with dichloride 1a, under
the same conditions used with 6d, afforded the benzothiadiazine

N,N-Dialkyl-N0-Chlorosulfonyl Chloroformamidines. XV
E
R1
R1
H
N
NH2
NMe2
NMe2
R2
O
O
R2
1a
S
N
N
N
H
N
H
S
R2
R2
R1
R1
6
O
O
9
8
R1
O
Me2N
R1
Me
N
N
R1
S
N
O
N
N
S
N
N
O
O
R2
R2
17
R2
14
NMe2
Scheme 9.
Table 1. Synthesis of benzo[e][1,2,4]thiadiazine dioxides 8, bis-adducts 9, [1,3,2,4,6]dithiatriazine tetraoxides 17, triazines 14, and other products
from anilines 6
Method A: Et3N/CH2Cl2; Method B: DMPU, 808C; Method C: iPr2NEt (after 30 min)/CH2Cl[28]
Products
(Yields [%])
R1
R2
Method
A
8
9
17
14
Other product(s)
H
4-Et (6c)
H (6b)
8b (29)
9b (32)
NCCH2
A
B
14c (13)
14c (12)
15 (5)
Bn
H (6d)
A
B
8d (14)
8d (3)
17d (66)
14dA (6)
18 (13)
19 (61)
Ph
H (6e)
A
A
A
A
8e (35)
17e (20)
17f (32)
17g (10)
17h (39)
14eB (7)
14f (3)
14g (2)
Fused Ph (1-naphthalene) (6f)
9f (25)
Me
Me
H
3-Me (6g)
8g (14)
6-Me (6h)
Not possible
3-OMe (6i)
A
C
8i (12)
8i (71)
24(1), 25(2)
H
H
4-OMe (6j)
3-Br (6k)
A
C
8j (23)
8j (40)
9j (20)
9k (86)
14jA (3)
A
C
17k (8)
27(4), 28(14)
8k (4)
8k þ 8l (10)
AIsolated as HBr salt.
BIsolated as HI salt.
8e and the [1,3,2,4,6]dithiatriazine tetraoxide 17e (Scheme 9,
Table 1). The triazine 14e was isolated from the aqueous layer
(as described above for 14d) and crystallised as the hydroiodide
salt. Similar treatment of 1-aminonaphthalene 6f provided the
bis-adduct 9f, dithiatriazine tetraoxide 17f, and the triazine
14f. The crystal structures of 14d, 14f, 18, and 19 are shown
in Figs 4, 5, and in the Supplementary Material.
The reaction of 2,3-dimethylaniline 6g with dichloride 1a
under the Et3N/CH2Cl2 conditions (Method A) afforded the
benzothiadiazine dioxide 8g and the dithiatriazine tetraoxide
17g. Similar reaction of 2,6-dimethylaniline 6h with dichloride
1a provided the dithiatriazine tetraoxide 17h as the only isolated
product (Scheme 9, Table 1). In this case, both ortho carbon
atoms of the aniline substrate 6h are substituted, so formation of
the benzothiadiazine 8 is precluded. The structures of 8e, 8g,
17g, and 17h were confirmed by X-ray crystallography (Fig. 6
and Supplementary Material).
Fig. 5. ORTEP diagram of the triethylammonium [1,3,2,4,6]dithiatriazin-2-ide
salt 18.

F
D. Innes et al.
Fig. 6. ORTEP diagrams of 17g (left), and 17h (right). One 2,3-dimethylphenyl substituent of 17g (C1–C8) was modelled as disordered over two
positions, with the two components related by an ,1808 rotation about the N–C bond. Only the major component is shown.
H
Cl
S
Cl3C
CCl3
N
i-Pr2 NEt or Et3N
NH2
R
Cl
O
ꢀ
R
CH2Cl2
0ꢁC, 15 min
N
N
S
O
6
O
O
21
20
H
N
Me
Me
N
CCl3
i-Pr2NEt
CCl3
10
AlCl3
N
N
S
O
N
CH2Cl2
0ꢁC, 15 min
CH2Cl2
rt, 30 min
Me
Cl
S
O
O
O
22
23
Scheme 10.
H
N
At an advanced stage of this work, we noted a publication
NMe2
from Shalimov and coworkers[8] that reported a very closely
related study of the reactions of anilines 6 with dichloride 1a and
the previously unknown (Z)-2,2,2-trichloro-N-(chlorosulfonyl)
acetimidoyl chloride (20), under similar conditions to those in
our study, which provided the benzothiadiazines 8 and 21
(Scheme 10) respectively. Surprisingly, their paper did not
report the isolation of any of the side products we isolated;
however, they reported that a reaction between N-methylaniline
10 and the imidoyl chloride 20 in CH2Cl2 in the presence of
iPr2NEt gave the amidine 22.[8] This could be due to the large
difference in reaction time, as the Shalimov reaction was
allowed to proceed for only 15 min at 08C, whereas our reaction
proceeded for 3 days at rt. Shalimov et al. also demonstrated that
compound 22 underwent an AlCl3-mediated Friedel–Crafts type
cyclisation to give the benzothiadiazine 23 (Scheme 10).[8]
The Shalimov paper prompted us to examine some aniline
substrates from that work.[8] The reaction between 3-methox-
yaniline (6i) and the dichloride 1a under similar conditions
(Et3N/CH2Cl2, rt) to those used for substrates 6b–h gave a
complex mixture of products, which provided the benzothiadia-
zine 8i as well as the the known urea 24[9] and the unusual adduct
25 all in quite low yields (Shalimov[8] reported a 71 % yield for
8i). A similar reaction with 4-methoxyaniline (6j) provided the
benzothiadiazine 8j, albeit in lower yield (23 %) than reported
by Shalimov and coworkers (40 %),[8] as well as the bis-adduct
9j (20 %).
.HCl
N
Cl
S
O
R
O
26
Fig. 7. Structure of intermediate 26.
In order to address the variation in outcomes between use of
our conditions and those employed by Shalimov and coworkers,
we treated 3-methoxyaniline with dichloride 1a under the
reported conditions.[8] Only the benzothiadiazine 8i was iso-
lated. This led us to consider the differences between the two
sets of conditions. Shalimov and coworkers used a 1 : 1 ratio of
aniline substrate to dichloride and a mixture of these two
compounds was stirred at rt for 30 min before the addition of
the amine base. We employed an excess of crude dichloride and
had the base present at the commencement of the experiment.
Additionally, the Shalimov conditions involved a 4-fold lower
concentration of reactants. Presumably, use of only one molar
equivalent of dichloride, relatively dilute conditions, and the
initial absence of base allows the formation of the ‘tethered’
intermediate hydrochloride salt 26 (Fig. 7) and avoidance or
minimisation of side-reactions, such as ‘bis-additions’ to the
dichloride 1a.
Delayed addition of base to the reaction mixture may facili-
tate the ring closure of 26 to the benzothiadiazine 8.

N,N-Dialkyl-N0-Chlorosulfonyl Chloroformamidines. XV
G
MeO
O
NMe2
Br
NMe2
H
N
NMe2
O
X
N
HN
S
N
S
NMe2
N
N
N
O
O
O
S
O
S
O
N
N
24 X ꢃ MeO
27 X ꢃ Br
O
Me2N
Br
Cl
O
28
25
OMe
Fig. 8. Structures of compounds 24, 25, 27, and 28.
resulting in intermediate J. Ring closure of J involving loss of
dimethylcyanamide and HCl as shown would afford dithiatria-
zine 17.
An alternative pathway to compounds 17 was identified by
stirring a mixture of sulfamide 16 and dichloride 1a in CH2Cl2 in
the presence of Et3N. This procedure provided the dithiatriazine
tetraoxide 17d in good yield, suggesting that the sulfamide 16
could act as an intermediate in the formation of dithiatriazine
tetraoxides 17 as shown in Scheme 12.
A proposed mechanism of formation for compound 18 and
ureas 24 and 27, presented in Scheme 13, was also inspired by
the isolation of compound 25 (Fig. 8). In the presence of an
excess of dichloride 1a, a second dichloride molecule could
react with an NH moiety of the bis-adduct 9, resulting in
intermediate K. Ring closure of K with loss of HCl would
afford intermediate L. Hydrolytic cleavage of L by hydroxide
ion would liberate the stabilised anion 18 and the corresponding
urea (24, 27).
Fig. 9. ORTEP diagram of dithiatetrazocine 28.
We noted Shalimov’s comment ‘the chloroformamidine (1a)
did not give the target (benzo)thiadiazines upon interaction with
anilines containing electron-withdrawing substituents in the
benzene ring, even after prolonged refluxing in toluene in the
presence of diisopropylethylamine’, and therefore considered it
to of interest to evaluate the reaction between 3-bromoaniline 6k
(as a representative moderately electron-poor aniline) and the
dichloride 1a. Shalimov’s conditions afforded low yields of the
two possible benzothiadiazine isomers 8k and 8l, and a high
yield of the bis-adduct 9k (Scheme 10, Table 1). For compari-
son, the reaction was repeated under the conditions employed
with anilines 6b–h and this provided the dithiatriazine tetra-
oxide 17k, the known urea 27,[10] and, interestingly, the unusual
eight-membered ring compound 28 as the major product (22 %
yield)(Fig. 8). The structures of 8k, 17k, and 28 were confirmed
by X-ray crystallography (Fig. 9 and Supplementary Material).
The [1,3,2,4,6]dithiatriazine ring system of compounds 17
(Scheme 9) is known but rare.[11–13] The eight-membered ring
system of 28 has also been reported.[11,14–16] A possible mecha-
nism for formation for compounds 17, presented in Scheme 11,
was proposed in the light of the isolation of compound 25. In the
presence of excess of dichloride 1a, a second dichloride mole-
cule could react with the amidine NH moiety of the bis-adduct 9,
In the 1H and 13C NMR spectra for dithiatriazine 17g,
additional resonances were observed, which were indicative of
a slow rotation of the N(CH3)2 moiety about the N–C bond on
the NMR time scale (Fig. 10). This was confirmed by variable-
temperature NMR measurements. At higher temperature (658C)
in CD3CN, the two peaks at 3.18 and 2.70 ppm merged to a
single broad resonance at 2.99 ppm. Similar phenomena have
been observed many times during our studies of related sys-
tems.[1] Secondary splitting of the N(CH3)2 resonances of 17g
was observed at reduced temperatures (,158C), which indicates
a second slow exchange process is occurring due to the slow
rotation of one of the 2,3-dimethylphenyl rings about the N–C
bond. This result is consistent with observations noted during
X-ray crystallographic analysis of 17g – see Fig. 6.
1
Variable-temperature H NMR analysis of 17h (Table 1,
Fig. 10) indicated that the N(CH3)2 resonance of this molecule is
also subject to a slow rotation effect about the N–C bond on the
NMR time scale. At ambient temperatures in CD3CN, the two
peaks at 3.18 and 2.44 ppm merged to a single broad resonance
at 2.87 ppm. Line shape analyses[17–20] of the spectra from 17g
NMe2
Cl
Cl
Cl
NMe2
O
N
R
Me2N
1a
N
S
N
O
O
S
N
S
O
– Me2N–CN
– HCl
S
O
N
O
N
H
H
N
H
N
R
O
O
N
N
S
N
S
O
O
Me2N
R
R
R
R
17
O
O
Me2N
9
J
Scheme 11.

H
D. Innes et al.
O
Me2N
N
S
S
N
O
H
N
H
N
1a
Et3N
N
S
O
O
O
Bn
O
Bn
CH2Cl2, rt
(63 %)
Bn Bn
17d
16
– HCl
O
S
NMe2
Cl
Cl
N
S
O
O
O
NMe2
S
N
S
Cl
H
N
H
N
H
N
– HCl
N
O
O
O
O
Bn Bn
Bn Bn
Scheme 12.
Cl
S
Cl
O
O
O
S
N
Me2N
N
S
S
ꢂ
OH
Me2N
O
N
S
N
S
1a
O
O
N
– HCl
N
N
N
Me2N
Cl
N
O
O
NH
O
O
NMe2
H
N
H
N
Me2N
R
R
L
R
K
R
R
R
O
O
NMe2
9
HO
N
O
Me2N
R
R
N
O
S
N
Me2N
ꢂ
N
ꢀ
S
O
O
H
N
R
O
18
R ꢃ 2-Bn,
Et3NHꢀ salt
24
27
R ꢃ 3-MeO
R ꢃ 3-Br
Me2N
Scheme 13.
Me
Me
give various products, some of them quite unexpected. The
structure of the benzo[e][1,2,4]thiadiazine dioxides 8, from 1,3-
NCC bis-nucleophilic substitution, was confirmed by X-ray
crystallography, thereby correcting an earlier structural mis-
assignment.[4] Formation of benzothiadiazine 8 is favoured with
electron-rich anilines and the stepwise synthetic protocol (with
delayed addition of base) developed by Shalimov and cow-
orkers.[8] The reactions of anilines bearing ortho-substituents
with an excess of dichloride 1a provided reduced yields of the
benzothiadiazines 8, with the bis-anilino adducts 9 or the
unusual dithiatriazine tetraoxides 17 as the major products and,
on occasion, remarkably, low yields of the triazines 14. The
reaction of 3-bromoaniline with an equimolar amount of
dichloride 1a (with delayed addition of base) afforded low
yields of the two isomeric benzothiadiazines 8 and a high yield
of the bis-anilino adduct 9k. An excess of 1a with the same
substrate provided the eight-membered ring product 28 as the
major product as well as the dithiatriazine tetraoxide 17k.
Mechanistic pathways were proposed to account for the various
unexpected products isolated. Such uncommon heterocyclic
structures are sought after for bioactive molecule discovery
screening programs.
Me
Me
O
O
Me
Me
N
N
N
S
N
Me
O
S
N
O
S
N
Me
N
N
S
O
O
O O
Me
Me Me
Me
17h
17g
Fig. 10. Rotation of N(CH3)2 moieties of 17g and 17h and rotation of aryl
substituent of dithiatriazine 17g.
and 17h provided rates and activation parameters for all of these
processes (see the Supplementary Material for details). Extra or
broadened signals in the NMR spectra for other dithiatriazines
17 suggested that similar restricted rotation phenomena also
occurred with these molecules.
Conclusions
The bis-electrophilic N,N-dimethyl-N0-chlorosulfonyl chlor-
oformamidine 1a underwent reactions with a range of anilines to

N,N-Dialkyl-N0-Chlorosulfonyl Chloroformamidines. XV
I
Experimental
3-(Dimethylamino)-7-ethyl-4H-benzo[e][1,2,4]thiadiazine
1,1-Dioxide 8b
Methods and Materials
Et3N (0.2mL, 1.4 mmol) was added toa solutionofthe bis-adduct
9b (195mg, 0.5 mmol) and the dichloride 1a (140mg, 0.7 mmol)
in 1,2-dichloroethane (1mL) at 08C and the resulting mixture was
stirred at 508C overnight. The reaction mixture was cooled to rt
and water (5mL) was added with stirring. The aqueous phase was
extracted with CH2Cl2 (3ꢀ 10mL). The combined extract was
dried and the solvent was evaporated. Purification by chroma-
tography over silica gel (40 % EtOAc in hexanes) gave the title
compound 8b (25 mg, 19%) as a white solid.
Reactions were carried out under an atmosphere of nitrogen.
Dichloromethane and triethylamine were distilled over calcium
hydride. THF was distilled over sodium benzophenone ketyl.
Other reagents were used as received. Dichloride 1a was pre-
pared as described earlier.[1] Analytical thin-layer chromatog-
raphy was performed on aluminium-backed silica sheets,
visualised with UV light, and developed with ninhydrin dip.
Organic extracts were dried over anhydrous Na2SO4. Chroma-
tography was performed on 230–400-mesh silica (particle size:
1
0.04–0.063 mm). H and 13C NMR spectra were recorded in
N-((Dimethylamino)(methyl(phenyl)amino)methylene)-N0-
methyl-N0-phenyl sulfamide 11
DMSO-d6 solution (unless otherwise specified) on a Bruker
Ultrashield 600 spectrometer (600 and 150 MHz respectively),
except for spectra for 8b, 9b, 9f (1H), 17e, and 28, which were
recorded on a Bruker Ultrashield 400 spectrometer. Chemical
shifts (d) were measured in parts per million. 1H NMR chemical
shifts were referenced to d 7.26 for CDCl3, 2.50 for DMSO-d6
and 1.94 for CD3CN. 13C NMR chemical shifts were referenced
to d 77.16 for CDCl3, 39.52 for DMSO-d6 and 118.26 for
CD3CN. Spectroscopic data are reported using the following
format: (1) chemical shift (ppm); (2) integration; (3) multiplicity
(s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet, dd ¼ doublet of
doublets, m ¼ multiplet, br ¼ broad); (4) coupling constant
J (Hz); (5) assignment. Melting points were determined using a
Stanford Research Systems Digimelt MPA161 and are uncor-
rected. High-resolution mass spectrometry was performed using
a Waters Synapt HDMS instrument using electrospray ionisa-
tion, positive ion with lockspray (calibration: infusion of
0.5 mM sodium formate solution) or a PerkinElmer AxION
DSA-ToF system (calibration: infusion of Agilent Technologies
APCI/APPI Tuning mix, product number: G2432A).
A mixture of N-methylaniline 10 (1.61 g, 15 mmol) and Et3N
(3.0 g, 30 mmol) in CH2Cl2 (10 mL) was added to a cooled
solution of the dichloride 1a (3.0 g, 15 mmol) in CH2Cl2 (20 mL)
and the reaction mixture stirred at rt for 3 days. Water (20 mL)
was added with stirring. The aqueous phase was extracted with
CH2Cl2 (3 ꢀ 20 mL). The combined organic phase was dried
and the solvent was removed under vacuum. The residue was
purified by chromatography over silica gel (CH2Cl2) to give the
title compound 11 (2.61 g, 48 %) as flat, colourless needles
following crystallisation from aqueous iPrOH, mp 109–1108C.
m/z 347.1537 [M þ H]þ; C17H23N4O2S requires [M þ H]þ
347.1547). dH 7.47–7.41 (2H, m, ArH), 7.35 (2H, t, J 7.8, ArH),
7.28–7.18 (3H, m, ArH), 7.04–6.93 (1H, m, ArH), 6.72 (2H, d,
J 7.9, ArH), 3.18 (2 ꢀ s, 2 ꢀ NCH3), 2.71 (6H, s, N(CH3)2). dC
158.81, 144.60, 143.61, 129.20, 128.36, 125.46, 125.06, 122.22,
118.53, 38.85, 38.79, 37.87.
(Z)-2-(2-((4-(Dimethylamino)-1-methyl-1,3,5-triazin-2(1H)-
ylidene)amino)phenyl)acetonitrile 14c and 2-
(Dimethylamino)quinazolin-4(3H)-one 15[3]
3-(Dimethylamino)-7-ethyl-4H-benzo[e][1,2,4]thiadiazine
1,1-Dioxide 8b and N-((Dimethylamino)((4-ethylphenyl)
amino)methylene)-N0-(4-ethylphenyl)sulfamide 9b
Method B: A mixture of 2-(2-aminophenyl)acetonitrile 6b
(300 mg, 2.3 mmol) and the dichloride 1a (800 mg, 3.9 mmol) in
DMPU (5 mL) was heated at 808C for 16 h. The crude reaction
mixture was diluted with an aqueous solution of citric acid
(15 %, 30 mL) and extracted with CH2Cl2 (3 ꢀ 30 mL). The
aqueous layer was adjusted to pH 10 by addition of NaOH (5 M)
and the resulting cloudy solution extracted with EtOAc
(3 ꢀ 20 mL). The combined organic phase was dried and the
solvent was evaporated under vacuum to give a brown solid,
which was purified via chromatography over silica gel. Elution
with 10 % MeOH in CH2Cl2 gave the title compounds 14c
(65 mg, 12 %) and 15 (20 mg, 5 %) as white solids.
Method A: Et3N (0.6 ml, 3.4 mmol) was added dropwise to a
stirred solution of 2-(2-aminophenyl)acetonitrile 6b (300 mg,
2.3 mmol) and the dichloride 1a (660 mg, 3.2 mmol) in CH2Cl2
(4 mL) at 08C and the resulting mixture was stirred at rt
overnight. The reaction mixture was extracted with EtOAc
(3 ꢀ 20 mL). The aqueous phase was adjusted to pH 10 by
addition of NaOH (5 M) to provide the title compound 14c
(93 mg, 13 %) as a tan solid.
A mixture of 4-ethylaniline 6c (2.42 g, 20 mmol) and Et3N
(4.0 g, 40 mmol) in CH2Cl2 (10 mL) was added over 5 min to a
cooled solution of the dichloride 1a (4.1 g, 20 mmol) in CH2Cl2
(25 mL). The mixture was stirred at rt for 6 h and then water
(100 mL) and Et2O (60 mL) were added sequentially. After
stirring for 4 h, the crystalline matter was filtered off and washed
lightly with Et2O to afford the title compound 8b (1.47 g, 29 %)
as colourless needles. The organic layer of the filtrate was
evaporated and the residue was purified by chromatography
over silica gel (CH2Cl2) to give the title compound 9b (2.44 g,
32 %) as colourless needles following crystallisation from
cyclohexane.
8b: Recrystallised from MeOH, mp 300–3028C. m/z 254.0967
[Mþ H]þ; C11H16N3O322S requires [Mþ H]þ 254.0963. dH
(400 MHz) 10.24 (1H, s, NH), 7.43 (1H, s, ArH), 7.36 (2H, m,
ArH), 3.05 (6H, s, N(CH3)2), 2.61 (2H, q, J 7.6, CH2CH3), 1.17
(3H, t, J 7.6, CH2CH3). dC (100 MHz) 151.12, 139.81, 133.91,
131.77, 122.80, 120.78, 117.50, 37.44, 27.38, 15.42.
9b: Recrystallised from cyclohexane, mp 116–1188C. m/z
375.1858 [M þ H]þ; C19H27N4O322S requires [M þ H]þ
375.1855). dH (400 MHz) 9.20 (1H, s, NH), 8.32 (1H, s, NH),
7.07 (2H, d, J 8.9, ArH), 7.01 (4H, s, ArH), 6.72 (2H, d, J 8.6,
ArH), 2.60 (6H, s, N(CH3)2), 2.56–2.43 (4H, m, 2 ꢀ CH2CH3),
1.12 (3H, t, J 7.6, CH2CH3); 1.10 (3H, t, J 7.6, CH2CH3). dC
(100 MHz) 155.93, 139.80, 138.27, 137.61, 137.29, 128.76,
128.39, 121.25, 119.64, 38.94, 27.87, 16.05, 15.93.
14c: Recrystallisation from CH2Cl2/MeOH gave clear, col-
ourless blocks, mp 137–1388C. m/z 269.1514 [M þ H]þ;
C14H17N6 requires [M þ H]þ 269.1515. dH 8.27 (1H, s, triazine
CH), 7.52 (1H, dd, J 8.1, 0.9, ArH), 7.26 (1H, d, J 7.5, ArH), 7.18
(1H, td, J 7.7, 1.5, ArH), 6.88 (1H, td, J 7.4, 1.3, ArH), 3.79 (2H,
s, CH2CN), 3.39 (3H, s, NCH3), 3.10 (3H, s, NCH3), 2.94 (3H, s,
NCH3). dC 160.80, 158.16, 147.72, 147.20, 128.19, 127.49,
124.43, 122.76, 121.01, 119.53, 36.19, 36.05, 35.69, 19.85.

J
D. Innes et al.
15: Recrystallisation from acetone gave colourless blocks,
14d: Colourless prisms, mp 209–2118C. m/z 320.1884 [M þ
H]þ; C19H22N5 requires [M þ H]þ 320.1875). dH 10.16 (1H, s,
NH), 8.57 (1H, s, CH), 7.40–7.31 (3H, m, ArH), 7.23 (1H, dd,
J 6.7, 1.3, ArH), 7.18 (2H, t, J 8.2, ArH), 7.13–7.07 (3H, m,
ArH), 3.96 (2H, s, CH2), 3.63 (3H, s, NCH3), 3.12 (3H, s,
NCH3), 2.72 (3H, s, NCH3). dC 159.71, 158.29, 153.30, 139.88,
138.61, 133.89, 130.61, 128.76, 128.64, 128.25, 128.09, 127.10,
125.73, 37.22, 36.78, 36.50, 36.29.
mp 242–2438C. m/z 190.0980 [M þ H]þ; C10H12N3O requires
[M þ H]þ 190.0980). dH 7.88 (1H, dd, J 7.9, 1.6, ArH), 7.62–
7.52 (1H, m, ArH), 7.31 (1H, d, J 8.3, ArH), 7.13 (1H, t, J 7.4,
ArH), 3.09 (6H, s, N(CH3)2). dC 164.39, 163.31, 152.08, 134.60,
134.31, 126.29, 122.33, 116.45, 37.68.
18: Tan solid, mp 178–1798C. m/z 395.0853 [M þ H]þ;
C16H19N4O4S2 requires [M þ H]þ 395.0842). dH 8.95 (1H, s,
NH), 7.31 (2H, t, J 7.6, ArH), 7.27–7.15 (5H, m, ArH), 6.95 (2H,
ddd, J 16.0, 7.4, 2.3, ArH), 4.20 (1H, d, J 16.3, CHAHB), 4.09
(1H, d, J 16.3, CHAHB), 3.09 (6H, q, J 7.3, (Et3N), 2.60 (6H, s, N
(CH3)2), 1.17 (9H, t, J 7.3, (Et3N). dC 154.05, 140.59, 139.96,
138.30, 130.08, 129.53, 128.35, 127.30, 127.02, 126.69, 126.09,
45.71 (Et3N), 37.33, 36.03, 8.63 (Et3N).
5-Benzyl-3-(dimethylamino)-4H-benzo[e][1,2,4]
thiadiazine 1,1-Dioxide 8d, 2,4-Bis(2-benzylphenyl)-5-
(dimethylamino)-2H,4H-1,3,2,4,6-dithiatriazine 1,1,3,3-
Tetraoxide 17d, (Z)-4-((2-Benzylphenyl)imino)-N,N,5-
trimethyl-4,5-dihydro-1,3,5-triazin-2-amine Hydrobromide
14d, and Triethylammonium 4-(2-Benzylphenyl)-5-
(dimethylamino)-4H-1,3,2,4,6-dithiatriazin-2-ide 1,1,3,3-
Tetraoxide 18
Method A: A mixture of 2-benzylaniline 6d (2.0 g, 10.9 mmol)
and Et3N (6.6 mL, 47.3 mmol) in CH2Cl2 (8 mL) was added to a
stirred solution of the dichloride 1a (4.0 g, 19.5 mmol) in
CH2Cl2 (16 mL) at 08C. The reaction mixture was warmed to rt
and stirred for 3 days. Water (100 mL), Et2O (50 mL), and
EtOAc (50 mL) were added and the mixture stirred vigorously
for 30 min. The resulting precipitate was collected by filtration
and recrystallised from CH2Cl2 to give the title compound 18
(360 mg, 13 %) as colourless blocks.
The aqueous phase of the filtrate was treated with solid
Na2CO3 (5 g) and NaOH (5 g) with stirring until complete
dissolution. The mixture was extracted with Et2O (2 ꢀ 50 mL),
dried, and the solvent was removed under vacuum to give the
crude triazine (256 mg) as a colourless solid. The solid was
dissolved in a mixture of EtOAc (3 mL) and Et2O (4.5 mL) and a
solution of HBr in AcOH (50 %, 300 mg) was added. MeCN was
added until a clear solution was obtained. Et2O was added until
the mixture became faintly turbid and the mixture was left to
stand at ambient temperature overnight. The resulting crystals
were collected by filtration, affording the triazine HBr salt 14d
(281 mg, 6 %) as colourless prisms.
The organic phase of the original filtrate was washed with a
solution of citric acid (15 %, 30 mL), dried, and the solvent was
removed under vacuum. Purification of the residue by chroma-
tography over silica gel (15 % EtOAc in CH2Cl2) gave the
benzothiadiazine dioxide 8d (480 mg, 14 %) and the dithiatria-
zine tetraoxide 17d (2.01 g, 66 %) as white solids.
8d: White solid, mp 2308C (dec.). m/z 316.1128 [M þ H]þ;
C16H18N3O2S requires [M þ H]þ 316.1120). dH 9.31 (1H, s,
NH), 7.61 (1H, dd, J 7.8, 1.4, ArH), 7.43 (1H, dd, J 7.6, 1.5,
ArH), 7.30 (3H, td, J 7.7, 1.9, ArH), 7.22 (1H, t, J 7.4, ArH), 7.12
(2H, d, J 7.4, ArH), 4.29 (2H, s, CH2), 2.87 (6H, s, N(CH3)2). dC
152.36, 138.42, 133.79, 133.51, 129.20, 128.61, 128.46, 126.49,
125.36, 124.26, 120.80, 37.42, 35.61.
5-Benzyl-3-(dimethylamino)-4H-benzo[e][1,2,4]
thiadiazine 1,1-Dioxide 8d and (E)-2-(2-Benzylphenyl)-
1,1-dimethylguanidine 19
Method B: A mixture of 2-benzylaniline 6d (2.0 g, 10.9 mmol)
and the dichloride 1a (4.0 g, 19.5 mmol) in DMPU (9 mL) was
heated at 808C for 3 days. The mixture was cooled to rt and water
(50 mL) was added. No precipitate was observed, so the mixture
was extracted with EtOAc (3 ꢀ 50 mL). The combined organic
phase was dried and the solvent was evaporated to give a brown
oily residue, which was purified by chromatography over silica
gel. Elution with 0–15 % EtOAc in CH2Cl2 gave the title com-
pound 8d (100 mg, 3 %) as a white solid. The aqueous phase was
treated with a 5 M aqueous NaOH solution until formation of a
tan precipitate. This was collected to afford the title compound
19 (1.7 g, 61 %) as a tan solid.
19: Recrystallised from acetone to give colourless needles,
mp 125–1268C. m/z 254.1655 [M þ H]þ; C16H20N3 requires
[M þ H]þ 254.1652). dH 7.24–7.16 (5H, m, ArH), 7.14–7.08
(1H, m, ArH), 7.06–7.01 (2H, m, ArH), 6.76 (1H, td, J 7.4, 1.3,
ArH), 6.66 (1H, dd, J 8.3, 1.3, ArH), 4.91 (2H, s, NH2), 3.79 (2H,
s, CH2), 2.87 (6H, s, N(CH3)2). dC 152.02, 149.43, 142.00,
134.21, 129.67, 128.76, 127.96, 126.74, 125.33, 122.45, 120.37,
37.42, 36.96.
On one occasion, after elution with CH2Cl2, N-(2-benzyl-
phenyl)-N0-(2-benzylphenyl)sulfamide 16d was isolated (11 %)
as a white powder. Recrystallisation from isopropanol afforded
colourless prisms, mp 117–1198C. m/z 451.1450 [M þ Na]þ;
C26H24N2O2S requires [M þ Na]þ 451.1456). dH 9.28 (2H, s,
2 ꢀ NH), 7.43 (2H, dd, J 8.1, 1.3, ArH), 7.24 (4H, dd, J 8.2, 6.9,
ArH), 7.21–7.13 (4H, m, ArH), 7.11–7.03 (6H, m, ArH), 6.92
(2H, dd, J 7.7, 1.6, ArH), 3.87 (4H, s, 2 ꢀ CH2). dC 140.11,
135.70, 135.40, 129.89, 129.12, 128.28, 126.59, 125.91, 125.36,
124.12, 35.71.
17d: White powder, mp 210–2128C. m/z 583.1437 [M þ
Na]þ; C29H28N4O4S2Na requires [M þ Na]þ 583.1450). dH 7.58
(1H, td, J 7.8, 1.5, ArH), 7.54–7.46 (1H, m, ArH), 7.42 (1H, td,
J 7.5, 1.4, ArH), 7.39–7.17 (10H, m, ArH), 7.16–7.00 (4H, m,
ArH), 6.86–6.81 (1H, m, ArH), 4.31–4.10 (3H, m, CH2 þ 0.5
CHAHB þ 0.5 CHAHB), 3.82 (0.5H, d, J 15.5, CHAHB), 3.71
(0.5H, d, J 15.5, CHAHB), 3.18 and 3.13 (3H, 2 br s, NCH3), 2.83
and 2.78 (3H, 2 br s, NCH3). dC 151.42, 150.20, 143.48, 143.08,
140.69, 140.39, 139.67, 139.38, 138.81, 138.44, 134.15, 133.89,
131.87, 131.81, 131.63, 131.13, 131.09, 130.83, 130.79, 130.57,
130.45, 129.48, 129.46, 129.34, 129.32, 129.12, 128.65, 128.58,
128.52, 128.47, 128.14, 128.13, 127.56, 127.33, 127.02, 126.61,
126.57, 126.29, 126.14, 126.01, 36.17, 36.11, 35.80, 34.89.
2,4-Bis(2-benzylphenyl)-5-(dimethylamino)-2H,4H-
1,3,2,4,6-dithiatriazine 1,1,3,3-Tetraoxide 17d (from
Sulfamide 16)
Et3N (0.2 mL, 1.4 mmol) was added to a solution of the sulfa-
mide 16 (150 mg, 0.35 mmol) and the dichloride 1a (100 mg,
0.5 mmol) in CH2Cl2 (0.5 mL) at 08C. The resulting mixture was
stirred at rt overnight. Water (5 mL) and Et2O (5 mL) were
added and the resulting precipitate was collected by vacuum
filtration. Purification by chromatography over silica gel (40 %
EtOAc in hexanes) gave the title compound 17d (123 mg, 63 %)
as a white solid.

N,N-Dialkyl-N0-Chlorosulfonyl Chloroformamidines. XV
K
3-(Dimethylamino)-5-phenyl-4H-benzo[e][1,2,4]thiadiazine
1,1-Dioxide 8e, 2,4-Di([1,10-biphenyl]-2-yl)-5-
(dimethylamino)-2H,4H-1,3,2,4,6-dithiatriazine 1,1,3,3-
Tetraoxide 17e, (Z)-4-(([1,10-biphenyl]-2-yl)imino)-N,N,5-
trimethyl-4,5-dihydro-1,3,5-triazin-2-amine Hydroiodide 14e
was dried and the solvent was removed under vacuum. The
residue was purified by chromatography over silica gel.
Elution with 0–25 % EtOAc in CH2Cl2 provided the title
compounds 17f (163 mg, 7 %) as a tan powder and 9f (491 mg,
25 % after recrystallisation from CH2Cl2/EtOH) as colourless
prisms.
A mixture of 2-phenylaniline 6e (2.0 g, 11.8 mmol) and Et3N
(6.6 mL, 47.3 mmol) in CH2Cl2 (8 mL) was added to a stirred
solution of the dichloride 1a (4.0 g, 19.5 mmol) in CH2Cl2
(16 mL) at 08C. The reaction was stirred at 08C for 1 h, then
warmed to rt and stirred for a further 3 days. Water (100 mL),
Et2O (50 mL), and EtOAc (50 mL) were added and the mixture
was vigorously stirred for 30 min. The organic phase was
washed with 15 % citric acid solution (60 mL), dried, and
the solvent was removed under vacuum. Purification of the
residual solid by chromatography over silica gel (2–10 %
EtOAc in CH2Cl2) gave the benzothiadiazine dioxide 8e
(35 %) and the dithiatriazine tetraoxide 17e (20 %) as white
powders.
The aqueous phase was treated as for 14d above to give the
crude triazine as a brown solid, which was dissolved in EtOAc
(5 mL). 4-Toluenesulfonic acid monohydrate (300 mg) was
added and the solution was left to stand at ambient temperature
overnight. No crystals were observed so EtOAc/Et2O (1 : 1,
5 mL), NaI (0.3 g), and water (8 mL) were added. The mixture
was left to stand at ambient temperature for 4 h, which provided
the triazine HI 14e (7 %) as yellow prisms.
8e: Colourless blocks (from CH2Cl2/iPrOH), mp 247–2498C.
m/z 302.0971 [M þ H]þ; C15H16N3O2S requires [M þ H]þ
302.0963. dH 9.24 (1H, s, NH), 7.71 (1H, dd, J 7.8, 1.5, ArH),
7.64–7.57 (2H, m, ArH), 7.54 (2H, t, J 7.7, ArH), 7.50 (1H, dd, J
7.6, 1.5, ArH), 7.49–7.45 (1H, m, ArH), 7.40 (1H, t, J 7.7, ArH),
3.00 (6H, s, N(CH3)2). dC 152.34, 136.49, 133.68, 132.64,
130.75, 129.32, 129.08, 128.53, 125.62, 124.73, 121.93, 37.54.
17e: colourless crystals from CH2Cl2/iPrOH, mp 218–2198C.
m/z 533.1330 [M þ H]þ; C27H25N4O4S2 requires [M þ H]þ
533.1312). dH (400 MHz, 1208C) 7.64 (1H, dd, J 8.0, 1.3,
ArH), 7.60–7.52 (2H, m, ArH), 7.49–7.44 (3H, m, ArH),
7.39–7.30 (8H, m, ArH), 7.30–7.20 (4H, m, ArH), 2.73 (6H, s,
N(CH3)2). dC (100 MHz, 1208C) 149.40, 143.68, 139.30,
137.34, 136.83, 132.39, 131.99, 131.13, 130.70, 129.64,
129.24, 128.59, 128.49, 128.40, 128.25, 128.16, 128.09,
127.85, 127.54, 127.44, 127.21, 127.01, 126.85, 126.62, 38.52.
14e: Yellow prisms, mp 2408C (dec.). m/z 306.1720 [M þ
H]þ; C18H20N5 requires [M þ H]þ 306.1719). dH 10.22 (1H, s,
NH), 8.53 (1H, s, CH), 7.53–7.45 (4H, m, ArH), 7.43–7.37 (4H,
m, ArH), 7.36–7.31 (1H, m, ArH), 3.53 (3H, s, NCH3), 3.13 (3H,
s, NCH3), 2.88 (3H, s, NCH3). dC 159.75, 158.47, 153.00,
138.68, 138.31, 132.35, 130.37, 128.50, 128.42, 128.39,
128.37, 128.12, 127.44, 36.73, 36.62, 36.54.
The aqueous phase was treated with an excess of Na2CO3 and
extracted with Et2O/CH2Cl2. The combined organic phase was
dried and the solvent was removed under vacuum. The residual
solid was recrystallised from iPrOH to give the title compound
14f (86 mg, 3 %) as tan prisms.
17f: Tan powder, mp .2608C. m/z 481.1030 [M þ H]þ;
C23H21N4O4S2 requires [M þ H]þ 481.0999). dH 8.33–8.17
(5H, m, ArH), 8.11 (3H, dt, J 8.2, 2.5, ArH), 8.04 (2H, dd, J
20.0, 8.2,, ArH), 7.98–7.81 (2H, m, ArH), 7.80–7.59 (8H, m,
ArH), 7.55–7.43 (2H, m, ArH), 7.37 (1H, ddd, J 8.2, 6.9, 1.1,
ArH), 7.21 (1H, dd, J 7.5, 1.2, ArH), 3.26 (6H, br s, N(CH3)2),
2.70 (6H, br s, N(CH3)2). dC 151.76, 150.51, 134.31, 134.21,
134.02, 132.68, 132.15, 131.96, 131.73, 131.49, 131.45, 131.08,
130.57, 130.47, 130.41, 129.77, 128.74, 128.28, 128.26, 128.21,
128.15, 128.03, 127.49, 127.34, 127.29, 127.24, 126.97, 126.83,
126.17, 125.89, 125.69, 125.16, 124.95, 123.08, 122.79, 122.75,
122.49, 25.48.
9f: Colourless prisms, mp 1438C (dec.). m/z 419.1553
[M þ H]þ; C23H23N4O2S requires [M þ Na]þ 419.1542). dH
(400 MHz) 9.50 (1H, s, NH), 8.66 (1H, s, NH), 8.21 (1H, d,
J 8.4, ArH), 7.96–7.82 (3H, m, ArH), 7.68 (2H, t, J 7.4, ArH),
7.62–7.37 (6H, m, ArH), 7.25 (1H, t, J 7.9, ArH), 6.43 (1H, d,
J 7.4, ArH), 2.58 (6H, s, N(CH3)2). dC (100 MHz) 156.59,
134.78, 134.54, 133.97, 133.77, 128.31, 127.97, 127.86,
126.71, 126.60, 126.54, 125.98, 125.68, 125.60, 125.50,
124.87, 124.54, 123.28, 121.54, 120.25, 118.46, 38.42.
14f: Tan prisms, mp 153–1548C. m/z 280.1566 [M þ H]þ;
C16H18N5 requires [M þ H]þ 280.1562). dH 8.29 (1H, s, CH),
8.26 (1H, d, J 8.3, ArH), 7.78 (1H, d, J 8.0, ArH), 7.49 (1H, dd, J
7.3, 1.4, ArH), 7.43–7.33 (4H, m, ArH), 3.49 (3H, s, NCH3),
3.08 (3H, s, NCH3), 2.85 (3H, s, NCH3). dC 160.83, 158.24,
147.96, 145.35, 133.91, 129.61, 127.35, 125.86, 125.14, 124.37,
124.02, 120.33, 117.16, 36.13, 35.95, 35.85.
3-(Dimethylamino)-5,6-dimethyl-4H-benzo[e][1,2,4]
thiadiazine 1,1-Dioxide 8g and 5-(Dimethylamino)-2,4-bis
(2,3-dimethylphenyl)-2H,4H-1,3,2,4,6-dithiatriazine
1,1,3,3-Tetraoxide 17g, and (Z)-4-((2,3-Dimethylphenyl)
imino)-N,N,5-trimethyl-4,5-dihydro-1,3,5-triazin-2-amine
Hydrobromide 14g
2,3-Dimethylaniline 6g (1 mL, 8 mmol) was added to a stirred
solution of the dichloride 1a (5.0 g, 25 mmol) in CH2Cl2
(15 mL). The solution was cooled to 08C and Et3N (7 mL,
50 mmol) was added dropwise with stirring. The resulting
mixture was stirred at rt overnight. Water (10 mL) and Et2O
(10 mL) were added to the reaction mixture. The mixture was
extracted with CH2Cl2 (3 ꢀ 30 mL) and EtOAc (3 ꢀ 30 mL).
The combined organic phase was dried and the solvent was
removed under vacuum. The residue was purified by chroma-
tography over silica gel. Elution with 60 % EtOAc in hexanes
provided the title compounds 8g (288 mg, 14 %) as a tan solid
and 17g (346 mg, 10 %) as a crystalline white solid. The aqueous
phase was adjusted to pH 10 by treatment with an aqueous
solution of NaOH (5 M) and extracted with CH2Cl2 (3 ꢀ 30 mL).
The organic extract was dried and the solvent was removed
under vacuum. Chromatography over silica gel (2 % MeOH in
N-((Dimethylamino)(naphthalen-1-ylamino)methylene)-N0-
(naphthalen-1-yl)sulfamide 9f, 5-(Dimethylamino)-2,4-di
(naphthalen-1-yl)-2H,4H-1,3,2,4,6-dithiatriazine 1,1,3,3-
Tetraoxide 17f, and (Z)-N,N,5-Trimethyl-4-(naphthalen-1-
ylimino)-4,5-dihydro-1,3,5-triazin-2-amine 14f
A mixture of the dichloride 1a (2.5 g, 12.2 mmol), 1-amino-
naphthalene 6f (1.4 g, 9.8 mmol), and Et3N (3 g, 29.6 mmol)
in CH2Cl2 (15 mL) was stirred at rt for 3 days. The resulting
mixture was poured into a stirred mixture of aqueous citric
acid (5 %, 100 mL), CH2Cl2 (30 mL), and EtOAc (50 mL).
The precipitate in the organic phase was collected by filtra-
tion to afford 17f (589 mg, 25 %) as a tan powder. The filtrate

L
D. Innes et al.
CH2Cl2) gave the crude triazine as a tan solid. The solid was
dissolved in EtOAc and a solution of HBr in AcOH (50 %, 3 mL)
was added. MeCN was added until a clear solution was obtained
and then Et2O was added until faintly turbid. The mixture was
left to stand overnight and the resulting colourless crystals were
collected by filtration to afford the triazine HBr salt 14g
(100 mg, 2 %) as colourless prisms.
8g: Recrystallisation from acetone gave clear colourless
blocks, mp 2128C (dec.). m/z 276.0782 [M þ Na]þ;
C11H15N3O322SNa requires [M þ Na]þ 276.0783. dH (CDCl3)
8.10 (1H, s, NH), 7.62 (1H, d, J 8.0, ArH), 7.06 (1H, d, J 8.0,
ArH), 3.02 (6H, s, N(CH3)2), 2.29 (3H, s, ArCH3), 2.15 (3H, s,
ArCH3). dC (CDCl3) 151.38, 150.31, 141.32, 133.14, 126.05,
123.34, 121.25, 120.59, 37.71, 20.82, 12.86.
17g: Recrystallisation from CH2Cl2 gave clear colourless
blocks, mp 1548C dec. m/z 459.1134 [M þ Na]þ;
C19H24N4O342S2Na requires [M þ Na]þ 459.1137). dH (CD3CN,
298 K) 7.45 (1H, d, J 8.0, ArH), 7.39–7.33 (4H, m, ArH), 7.33–
7.18 (5H, m, ArH), 7.03 (1H, t, J 7.8, ArH), 6.84 (1H, d, J 8.0,),
3.18 (6H, s, N(CH3)2), 2.70 (6H, s, N(CH3)2), 2.38 (3H, s,
ArCH3), 2.36 (3H, s, ArCH3), 2.36 (3H, s, ArCH3), 2.33 (3H, d, J
5.0), 2.32 (3H, s, ArCH3), 2.30 (3H, s, ArCH3), 2.24 (3H, s,
ArCH3), 1.95 (3H, s, ArCH3). dC (CD3CN, 248 K) 152.90,
151.34, 140.83, 140.59, 140.21, 139.82, 139.59, 137.90,
137.85, 135.29, 135.03, 132.83, 132.30, 132.01, 130.81,
130.27, 129.04, 128.50, 127.92, 127.55, 126.99, 126.83,
124.63, 124.42, 39.84, 39.73, 38.70, 38.67, 20.15, 20.14,
16.02, 15.90, 15.06, 14.07.
3-(Dimethylamino)-6-methoxy-4H-benzo[e][1,2,4]
thiadiazine 1,1-Dioxide 8i, 3-(3-Methoxyphenyl)-1,1-
dimethylurea 24,[9] and ((E)-(Dimethylamino)((N-((E)-
(dimethylamino)((3-methoxyphenyl)amino)methylene)
sulfamoyl) (3-Methoxyphenyl)amino)methylene)sulfamoyl
Chloride 25
3-Methoxyaniline 6i (1.5 mL, 13.35 mmol) was added to a
stirred solution of the dichloride 1a (4.2 g, 20 mmol) in CH2Cl2
(20 mL) at 08C. Et3N (5.6 mL, 40 mmol) was added and the
reaction mixture was stirred at rt overnight. Water (10 mL) was
added and the mixture was stirred for several hours. The
resulting precipitate was collected by filtration. The mother
liquor was extracted with CH2Cl2 (3 ꢀ 20 mL). The combined
organic extract was dried and the solvent was removed under
vacuum. The precipitate was purified by chromatography over
silica gel (40 % EtOAc in CH2Cl2), followed by recrystallisation
from MeOH/DMSO, affording the title compound 8i (400 mg,
12 %) as a white solid. Purification of the extract residue by
chromatography over silica gel (40 % Et2O in CH2Cl2) gave the
title compounds 24 (36 mg, 1 %) and 25 (72 mg, 2 %) as white
solids.
8i: Recrystallisation from CH2Cl2 gave colourless needles,
mp .2608C. m/z 278.0571 [M þ Na]þ; C10H13N3O3SNa
requires [M þ Na]þ 278.0575). dH 10.19 (1H, s, NH), 7.55
(1H, d, J 8.8, ArH), 7.00 (1H, d, J 2.3, ArH), 6.83 (1H, dd, J
8.8, 2.3, ArH), 3.81 (3H, s, OCH3), 3.08 (6H, s, N(CH3)2). dC
161.64, 150.99, 137.81, 124.25, 115.71, 111.44, 101.02, 55.55,
37.44.
24:[9] Recrystallisation from acetone gave colourless blocks,
mp 139–1418C (lit. mp 140–1428C[9]). m/z 217.0944 [M þ
Na]þ; C10H14N2O2Na requires [M þ Na]þ 217.0953). dH
(CDCl3) 7.18 (1H, t, J 2.3, ArH), 7.15 (1H, t, J 8.1, ArH),
6.83 (1H, ddd, J 8.1, 2.1, 0.9, ArH), 6.57 (1H, ddd, J 8.3, 2.6, 0.9,
ArH), 6.38 (1H, s, NH), 3.78 (3H, s, OCH3), 3.01 (6H, s, N
(CH3)2). dC (CDCl3) 160.28, 155.73, 140.65, 129.52, 111.88,
109.10, 105.30, 55.37, 36.57.
14g: Colourless prisms, mp .2608C. m/z 258.1716 [M þ
H]þ; C14H20N5 requires [M þ Na]þ 258.1719). dH 10.10 (1H, s,
HBr), 8.66 (1H, s, CH), 7.25–7.06 (3H, m, ArH), 3.69 (3H, s,
NCH3), 3.18 (3H, s, NCH3), 2.86 (3H, s, NCH3), 2.30 (3H, s,
ArCH3), 2.10 (3H, s, ArCH3). dC 160.15, 158.68, 153.22,
137.50, 133.75, 133.58, 129.01, 125.54, 125.18, 36.96, 36.62,
36.42, 20.01, 14.29.
25: A sample was recrystallised from CH2Cl2 to give colour-
less blocks, mp 134–1368C. m/z 569.1001 [M þ Na]þ;
C20H27N6O6S2ClNa requires [M þ Na]þ 569.1006. dH 8.63
(1H, s, NH), 7.26 (2H, td, J 8.1, 4.4, ArH), 6.93 (2H, td, J 8.1,
7.6, 2.2, ArH), 6.78 (1H, t, J 2.2, ArH), 6.73 (1H, t, J 2.3, ArH),
6.69 (2H, dt, J 7.9, 2.2, ArH), 3.74 (3H, s, OCH3), 3.60 (3H, s,
OCH3), 3.19 (3H, s, NCH3), 3.09 (3H, s, NCH3), 2.87 (6H, s, N
(CH3)2). dC 159.91, 159.11, 155.58, 146.59, 140.48, 138.84,
129.94, 129.09, 122.63, 115.75, 114.31, 113.04, 109.51, 106.59,
55.09, 54.98, 40.61, 40.58, 40.06, 39.01.
5-(Dimethylamino)-2,4-bis(2,6-dimethylphenyl)-2H,4H-
1,3,2,4,6-dithiatriazine 1,1,3,3-Tetraoxide 17h
Et3N (3.3 mL, 24 mmol) was added dropwise to a stirred
solution of the dichloride 1a (2.5 g, 12 mmol) and 2,6-dime-
thylaniline 6h (0.5 mL, 3.9 mmol) in CH2Cl2 (7 mL) at 08C.
The reaction mixture was warmed to rt and stirred overnight.
Water (5 mL) and Et2O (5 mL) were added and the resulting
white precipitate was collected by filtration. The mother liquor
was extracted with CH2Cl2 to give an orange residue, which
was purified by chromatography over silica gel. Elution with
20 % EtOAc in CH2Cl2 provided a white solid, which was
combined with the precipitate and further purified by chro-
matography over silica gel. Elution with 40 % EtOAc in hex-
anes provided the title compound 17h (330 mg, 39 %) as a
crystalline white solid.
3-(Dimethylamino)-7-methoxy-4H-benzo[e][1,2,4]
thiadiazine 1,1-Dioxide 8j, (Z)-((Dimethylamino)((4-
methoxyphenyl)amino)methylene)-N0-(4-methoxyphenyl)
sulfamide 9j, and (Z)-4-((4-Methoxyphenyl)imino)-N,N,5-
trimethyl-4,5-dihydro-1,3,5-triazin-2-amine 14j
17h: Recrystallisation from CH2Cl2 gave clear colourless
blocks,
mp
.2608C.
m/z
459.1127
[M þ Na]þ;
Et3N (3.5 mL, 25 mmol) was added to a stirred solution of 4-
methoxyaniline 6j (1 g, 8.1 mmol) and dichloride 1a (2.5 g,
12.2 mmol) in CH2Cl2 (20 mL) at 08C. The reaction mixture was
stirred at rt overnight. Water (20 mL) and Et2O (10 ml) were
added and the mixture was stirred vigorously for 30 min. The
resulting precipitate was collected by filtration. The mother
liquor was extracted with CH2Cl2 (3 ꢀ 20 mL), the combined
organic extract was dried, and the solvent was removed under
vacuum to give a brown, sticky residue. The precipitate was
purified by chromatography over silica gel (10 % EtOAc in
C19H24N4O342S2Na requires [M þ H]þ 459.1137. dH (328 K)
7.36 (1H, dd, J 8.4, 6.7, ArH), 7.31–7.26 (3H, m, ArH), 7.19–
7.14 (2H, m, ArH), 2.87 (6H, br. s, N(CH3)2), 2.40 (6H, s,
2 ꢀ ArCH3), 2.33 (6H, s, 2 ꢀ ArCH3). dH (CD3CN, 238 K)
7.35–7.31 (1H, m, ArH), 7.30–7.23 (3H, m, ArH), 7.16
(2H, d, J 7.6, ArH), 3.18 (3H, s, NCH3), 2.44 (3H, s, NCH3),
2.40 (6H, s, ArCH3), 2.33 (6H, s, ArCH3). dC (CD3CN, 238 K)
150.52, 142.00, 137.75, 133.65, 131.54, 130.71, 130.45, 130.33,
129.46, 40.47, 39.34, 19.49, 19.30.

N,N-Dialkyl-N0-Chlorosulfonyl Chloroformamidines. XV
M
CH2Cl2) to give the title compound 8j (480 mg, 23 %) as a white
solid. Purification of the extract residue by chromatography over
silica gel (10 % EtOAc in CH2Cl2) gave the title compound 9j
(305 mg, 20 %) as a white solid. The aqueous phase was adjusted
to pH 10 by treatment with an aqueous solution of NaOH (5 M)
and extracted with CH2Cl2 (3 ꢀ 30 mL). The organic extract was
dried and the solvent was removed under vacuum. Chroma-
tography over silica gel (2 % MeOH in CH2Cl2) gave the crude
triazine as a yellow solid. The solid was dissolved in EtOAc
and a solution of HBr in AcOH (50 %, 3 mL) was added. MeCN
was added until a clear solution was obtained and then Et2O was
added until the mixture became faintly turbid. The mixture was
left to stand at ambient temperature overnight and the resulting
colourless crystals were collected by filtration to afford the tri-
azine HBr salt 14j (50 mg, 3 %) as colourless prisms.
8j: White powder, mp .2608C. m/z 278.0570 [M þ Na]þ;
C10H13N3O3SNa requires [M þ Na]þ 278.0575). dH 10.20 (1H,
s, NH), 7.41 (1H, d, J 9.0, ArH), 7.17 (1H, dd, J 9.0, 2.8, ArH),
7.11 (1H, d, J 2.8, ArH), 3.79 (3H, s, OCH3), 3.08 (6H, s, N
(CH3)2). dC 155.52, 151.22, 129.61, 123.56, 119.95, 119.18,
104.74, 55.70, 37.42.
9j: White powder, mp 123–1258C. m/z 401.1257 [M þ Na]þ;
C17H22N4O4SNa requires [M þ Na]þ 401.1259). dH 9.00 (1H, s,
NH),8.26(1H, s, NH),7.12–6.98(2H,m, ArH), 6.87–6.77(4H,m,
ArH), 6.76–6.69 (2H, m, ArH), 3.72 (3H, s, OCH3), 3.69 (3H, s,
OCH3), 2.63 (6H, s, N(CH3)2). dC 155.92, 155.85, 155.25, 132.70,
132.44, 122.82, 121.58, 114.25, 114.02, 55.22, 55.12, 38.54.
14j: Colourless prisms, mp 2418C. m/z 260.1489 [M þ H]þ;
C13H18N5O requires [M þ Na]þ 260.1511). dH 10.04 (1H, s,
HBr), 8.66 (1H, s, CH), 7.43 (2H, d, J 8.9, ArH), 7.00 (2H, d,
J 8.9, ArH), 3.77 (3H, s, OCH3), 3.67 (3H, s, NCH3), 3.22 (3H, s,
NCH3), 3.04 (3H, s, NCH3). dC 160.15, 158.80, 157.42, 152.80,
128.25, 126.18, 113.83, 55.32, 37.08, 36.84, 36.79.
(1H, m, ArH), 7.63 (1H, t, J 8.1, ArH), 7.58–7.53 (1H, m,
ArH), 7.49 (1H, t, J 8.0, ArH), 7.29–7.23 (2H, m, ArH), 3.21
(3H, s, NCH3), 2.97 (3H, s, NCH3). dC 149.88, 136.47, 133.64,
133.38, 132.41, 132.19, 131.96, 131.58, 131.02, 129.42, 126.40,
122.41, 121.89, 39.17, 38.94.
27: A sample was crystallised from acetone to give colourless
blocks, mp 153–1548C. m/z 264.9946 [M þ Na]þ;
C9H11N2OBrNa requires [M þ Na]þ 264.9952. dH 8.43 (1H, s,
NH), 7.79 (1H, t, J 2.0, ArH), 7.46 (1H, ddd, J 8.2, 2.1, 1.0, ArH),
7.17 (1H, t, J 8.1, ArH), 7.08 (1H, ddd, J 7.9, 2.0, 1.0, ArH), 2.92
(6H, s, N(CH3)2). dC 155.36, 142.48, 130.17, 123.96, 121.63,
121.18, 118.09, 36.20.
N-((Dimethylamino)((3-bromophenyl)amino)methylene)-
N0-(3-bromophenyl)sulfamide 9k, 6-Bromo-3-
dimethylamino-4H-benzo[e][1,2,4]thiadiazine 1,1-
Dioxide 8k, and 8-Bromo-3-dimethylamino-4H-benzo[e]
[1,2,4]thiadiazine 1,1-Dioxide 8l
Method C: The procedure of Shalimov et al.[8] was employed.
Thus, a solution of 3-bromoaniline (0.6 mL, 5.5 mmol) in
CH2Cl2 (20 mL) was added to a stirred solution of the dichloride
1a (1 g, 4.9 mmol) in CH2Cl2 (20 mL). The mixture was stirred
i
at rt for 30 min. A solution of Pr2NEt (1.9 mL, 11 mmol) in
CH2Cl2 (5 mL) was added and the reaction mixture was stirred
for 1.5 h. The solvent was removed and the residue was treated
with 5 % aqueous HCl. The precipitate was collected and puri-
fied by chromatography over silica gel. Elution with 50 %
EtOAc in hexanes gave the title compound 9k (1.13 g, 86 %) as a
white solid. Further elution with 10 % EtOAc in CH2Cl2 gave
the title compound 8k (60 mg, 4 %) as well as a mixture of 8k and
8l (146 mg, 10 %).
9k: Tan powder, mp 173–1758C. m/z 474.9422 [M þ H]þ;
C15H17Br2N4O2S requires [M þ H]þ 474.9433. dH 9.63 (1 H, s,
NH), 8.65 (1 H, s, NH), 7.26 (1 H, q, J 2.0, ArH), 7.23 – 7.13
(3 H, m, ArH), 7.09 (2 H, d, J 9.7, ArH), 7.05 (1 H, dd, J 8.1, 2.2,
ArH), 6.81 (1 H, m, ArH), 2.73 (6 H, 2 ꢀ s, N(CH3)2). dC 154.56,
141.73, 141.40, 130.84, 130.66, 125.74, 124.24, 122.36, 121.79,
121.64, 120.11, 118.65, 116.71, 38.64.
8k: White solid, mp 1308C dec. m/z 325.9586 [M þ Na]þ;
C9H10BrN3O2SNa requires [M þ Na]þ 325.9575). dH 10.38
(1H, s, NH), 7.68 (1H, d, J 1.9 Hz ArH), 7.59 (1H, d, J 8.3,
ArH), 7.42 (1H, dd, J 8.3, 1.9, ArH), 3.09 (6H, s, N(CH3)2). dC
151.32, 138.16, 126.49, 124.64, 124.56, 122.02, 120.28, 37.47.
8k and 8l: White solid. m/z 325.9586 [M þ Na]þ;
C9H10BrN3O2SNa requires [M þ Na]þ 325.9575). dH 10.32
(1.5H, s, NH – 8k and 8l), 7.71 (0.5H, d, J 1.8, ArH – 8k),
7.60 (0.5H, d, J 8.3, ArH – 8k)), 7.54–7.37 (3.5H, m, ArH – 8k
and 8l), 3.09 (3H, s, N(CH3)2 – 8k); 3.09 (3H, s, N(CH3)2 – 8l).
dC 150.97, 149.01, 138.09, 137.55, 132.62, 129.22, 126.79,
124.71, 124.60, 122.14, 122.04, 120.05, 117.42, 116.98,
37.51, 37.35 (8l resonances in italics).
2,4-Bis(3-bromophenyl)-5-(dimethylamino)-2H,4H-
1,3,2,4,6-dithiatriazine 1,1,3,3-Tetraoxide 17k, 3-(3-
Bromophenyl)-1,1-dimethylurea 27, and (3Z,7Z)-2,6-Bis(3-
bromophenyl)-3,7-bis(dimethylamino)-2H,6H-1,5,2,4,6,8-
dithiatetrazocine 1,1,5,5-Tetraoxide 28
Method A: Et3N (4.2 mL, 30 mmol) was added to a stirred
solution of 3-bromoaniline 6k (1 mL, 9 mmol) and dichloride 1a
(3.0 g, 15 mmol) in CH2Cl2 (20 mL) at 08C. The reaction mix-
ture was stirred at rt overnight. Water (20 mL) was added and the
precipitate was collected by filtration, affording the title com-
pound 28 (400 mg, 14 %) as a white solid. The mother liquor was
extracted with CH2Cl2 (3 ꢀ 20 mL) and EtOAc (3 ꢀ 20 mL).
The combined organic extract was dried and the solvent was
removed under vacuum. The residue was purified by chroma-
tography over silica gel. Elution with 10 % EtOAc in CH2Cl2
gave the title compounds 17k (194 mg, 8 %) and 27 (98 mg, 4 %)
as white solids.
28: A sample was crystallised from DMF to give colour-
less blocks, mp 2338C dec. m/z 606.9410 [M þ H]þ;
C18H21Br2N6O4S2 requires [M þ H]þ 606.9427. dH (400 MHz)
7.50–7.44 (2H, m, ArH), 7.35–7.29 (4H, m, ArH), 7.10–7.02
(2H, m, ArH) 3.35 (6H, 2 ꢀ NCH3), 3.14 (6H, 2 ꢀ NCH3).
dC 152.77, 139.06, 130.83, 125.96, 121.64, 118.87, 115.31,
39.60, 38.76.
17k: A sample was crystallised from acetone to give colour-
less needles, mp 2058C (slow dec.). m/z 558.8733 [M þ Na]þ;
C15H14N4O4S2Br2Na requires [M þ Na]þ 558.8721. dH 7.91
(1H, t, J 2.0, ArH), 7.86–7.81 (1H, m, ArH), 7.79–7.74
X-Ray Crystallography
X-Ray crystallography for compounds 8e, 8g, 14c, 15, 17g, 17h,
17k, 18, 19, and 28 was performed at the Bragg Crystallography
Facility at The University of Adelaide. Single crystals suitable
for X-ray diffraction experiments were covered in Paratone-N oil
and mounted on a glass fibre. Data (2ymax 558) were collected at
150 K using an Oxford Diffraction X-Calibur X-ray diffractom-
eter and MoKa (l 0.71073 A) radiation. After integration and
scaling, the datasets were merged into N unique reflections (Rint).
The structures were solved using conventional methods and
˚

N
D. Innes et al.
refined by using full-matrix least-squares using the SHELX-14
software in conjunction with the X-Seed interface. Non-hydrogen
atoms were refined with anisotropic thermal parameters and
hydrogen atoms were placed in calculated positions.
X-Ray crystallography for compounds 8b, 14d.HBr, and 14f
was performed at Monash University. Representative crystals
were covered in a viscous oil and mounted on a cryoloop and
cooled to 123 K. Datasets were collected using an Oxford
Gemini Ultra (8b) or Bruker APEXII (14d.HBr and 14f) CCD
Dr Daniel Jardine (Flinders University) for mass spectrometry, and Dr Craig
Forsyth (Monash University) and Dr Chris Sumby (Bragg Crystallography
Facility, The University of Adelaide) for assistance with X-ray crystallog-
raphy. They are grateful to the CSIRO Biomedical Manufacturing Research
Program for financial support.
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ORTEP diagrams of crystal structures for benzothiadiazine
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triazine tetraoxide 17k, and side products 15 and 19; 1H and 13
C
NMR spectra of benzothiadiazine dioxides 8b–l, bis-anilino
adducts 9b–k, dithiatriazine tetraoxides 17d–k, triazines 14c–f,
and miscellaneous compounds 15, 16d, 18, 19, 24, 25, 27, and
28; and dynamic NMR calculations for dithiatriazine tetraoxides
17g and 17h are available on the Journal’s website.
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Conflicts of Interest
The authors declare no conflicts of interest.
[21] CrysAlisPro v1.171.35.15 2011 (Rigaku Oxford Diffraction:
Yarnton, UK).
Acknowledgements
[22] Apex2 v. 2014.7–1 2014 (Bruker AXS: Madison, WI).
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The authors thank Associate Professor Martin Johnston (Flinders Univer-
sity), and Dr Roger Mulder (CSIRO) for assistance with NMR spectroscopy,