Chlorosulfonation of some aldimine-isocyanate cycloadducts

Article abstract of DOI:10.1080/10426500390228611

Attempts to chlorosulfonate 1,4-diphenyl-1,3-diazetidin-2-one (1) failed, but the 3-methyl derivative (2) reacted with chlorosulfonic acid to give the bis-sulfonyl chloride (3), characterized as the sulfonamides 4 and 5. 2,3,6-Triphenyl-2,3-dihydro-1,3,5-thiadiazin-4-one (6) with chlorosulfonic acid suffered an acid-catalyzed ring-opening reaction forming the sulfonyl derivatives (8, 9) of N-phenyl-N′-thiobenzoylurea (7). Condensation of 8 and 9 with diethylamine afforded the diethyl-sulfonamide (10). Dibenzylideneethylenediamine (11) reacted with thiobenzoyl isocyanate at room temperature to yield the cycloadduct 12; however at 90°C, N,N′-di (thiobenzoylcarbamoyl)ethylenediamine (13) was obtained. The cycloadduct 12 with chlorosulfonic acid gave the ring-opened disulfonyl chloride 14 and the diethylsulfonamide 15. 1,6-Diphenylhexahydro-s-triazine-2,4-dione (17) was converted into the dimethyl derivative (18), which with chlorosulfonic acid afforded the bis-sulfonyl chloride (19), characterized as the sulfonamides 20-22.

Full text of DOI:10.1080/10426500390228611

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Phosphorus, Sulfur, and Silicon and the Related
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Chlorosulfonation of Some Aldimine-Isocyanate
Cycloadducts
Richard J. Cremlyn a , Richard M. Ellam a & Sultan Farouk a
a University of Hertfordshire , England
Published online: 23 Aug 2006.
To cite this article: Richard J. Cremlyn , Richard M. Ellam & Sultan Farouk (2003) Chlorosulfonation of Some
Aldimine-Isocyanate Cycloadducts, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:9, 1931-1941, DOI:
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Phosphorus, Sulfur, and Silicon, 178:1931–1941, 2003
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390228611
CHLOROSULFONATION OF SOME
ALDIMINE-ISOCYANATE CYCLOADDUCTS
Richard J. Cremlyn, Richard M. Ellam, and Sultan Farouk
University of Hertfordshire, England
(Received March 25, 2003)
Attempts to chlorosulfonate 1,4-diphenyl-1,3-diazetidin-2-one (1)
failed, but the 3-methyl derivative (2) reacted with chlorosulfonic acid
to give the bis-sulfonyl chloride (3), characterized as the sulfonamides
4 and 5. 2,3,6-Triphenyl-2,3-dihydro-1,3,5-thiadiazin-4-one (6) with
chlorosulfonic acid suffered an acid-catalyzed ring-opening reaction
forming the sulfonyl derivatives (8, 9) of N-phenyl-Nꢁ-thiobenzoylurea
(7). Condensation of 8 and 9 with diethylamine afforded the diethyl-
sulfonamide (10). Dibenzylideneethylenediamine (11) reacted with
thiobenzoyl isocyanate at room temperature to yield the cycloadduct
12; however at 90◦C, N,Nꢁ-di (thiobenzoylcarbamoyl)ethylenediamine
(13) was obtained. The cycloadduct 12 with chlorosulfonic acid gave
the ring-opened disulfonyl chloride 14 and the diethylsulfonamide 15.
1,6-Diphenylhexahydro-s-triazine-2,4-dione (17) was converted into the
dimethyl derivative (18), which with chlorosulfonic acid afforded the
bis-sulfonyl chloride (19), characterized as the sulfonamides 20–22.
Keywords: Chlorosulfonation; diazetidinone; hexahydro-s-thiazine-
dione; sulfonamides; thiadiazinone
Chlorosulfonic acid is a widely used reagent for the sulfonation and
chlorosulfonation of aromatic and heteroaromatic compounds.1 The
work described here continues our previous studies on the chlorosul-
fonation of heterocyclic compounds as a route to aryl-sulfonyl deriva-
tives of potential biological activity.1−4 In the present investigation we
studied the chlorosulfonation of some aldimine-isocyanate adducts con-
taining a cyclic urea grouping as a common structural feature, namely
a 1,3-diazetidinone, thiadiazinone, and a hexahydro-s-thiazinedione.
Thanks are due to the British Technology Group (BTG, Biosciences Division) for the
award of a research grant (SF); Dr. Richard A’Court (BTG) for his support and interest in
the project; Glaxo Group Research for the microanalyses; Smith Kline Beecham for the
FAB mass spectra.
Address correspondence to Richard M. Ellam, 4 Gomer Close, Hitchin, Herts SG4 8XP,
U.K.
1931

1932
R. J. Cremlyn et al.
DISCUSSION
1,4-Diphenyl-1,3-diazetidin-2-one (1) was prepared by reaction of iso-
cyanic acid on benzylideneaniline.5 Attempts to chlorosulfonate 1 by
treatment with excess chlorosulfonic acid (12 molar equivalents, or
3 molar equivalents in thionyl chloride) at room temperature (1 week),
or at 80◦C, were unsuccessful. The failure may be ascribed to hydrolytic
decomposition of the crude sulfonyl chlorides during the aqueous acidic
work-up procedures and resembles previous attempts to chlorosul-
fonate benzylidene-anilines.5 This argument is supported by the ob-
served instability of the diazetidinone (1) in both acidic and alkaline
media.6 Methylation of the diazetidinone (1) afforded the N-methyl
derivative (2) (Scheme 1), which is relatively stable under acidic condi-
tions. Hence, warming 2 with chlorosulfonic acid (6 molar equivalents)
in thionyl chloride at 50◦C gave the bis-sulfonyl chloride (3), charac-
terized by formation of the sulfonamides 4 and 5. The NMR spectral
data for the latter two compounds supported the proposed pattern of
para-sulfonation.
SCHEME 1
2,3,6-Triphenyl-2,3-dihydro-1,3,5-thiadiazin-4-one (6) was obtained
by cycloaddition of 2-phenylthiazoline-4,5-dione with benzylideneani-
line. Attempted chlorosulfonation of the cycloadduct 6 by treatment
with excess chlorosulfonic acid-thionyl chloride failed to yield the ex-
pected trisulfonyl chloride because the substrate underwent an acid-
catalyzed ring-opening reaction. This was confirmed by heating 6 with
ethanolic hydrochloric acid to give N-phenyl-Nꢁ-thiobenzoylurea (7)
(Scheme 2).
The cycloadduct 6, by reaction with excess chlorosulfonic acid (8 mo-
lar equivalents) in thionyl chloride at room temperature, appeared to

Chlorosulfonation
1933
SCHEME 2
yield a mixture of the bis-sulfonyl chloride (8) and the chlorosulfonyl
sulfonic acid (9) (Scheme 2). The same product mixture was obtained
when 6 was heated under reflux with a large excess of chlorosulfonic
acid (15 equivalents). This mixture of 8 and 9 was condensed with an
excess of diethylamine to yield the bis-diethylsulfonamide (10) after
two recrystallizations from ethanol.
Reaction of N-phenyl-Nꢁ-thiobenzoylurea (7) with excess chlorosul-
fonic acid gave the same product mixture of 8 and 9. The NMR spectral
data indicated the presence of a para-sulfonyl group in one aromatic
ring (AAꢁBBꢁ pattern) and a more complex aromatic proton resonance
pattern in the other ring, possibly indicative of ortho-sulfonation. The
broad resonance observed at ∂9.8 was reduced by D2O treatment and is
ascribed to the sulfonic acid group. The ortho-sulfonic acid (9) may have
arisen from sulfonation of the thiol tautomer of 7 to give the S SO3H
derivative. Suitable sulfonic and thiosulfonic acids can undergo acid-
catalyzed migration of the sulfonic acid group into a neighboring
aromatic nucleus, as was observed8 in the chlorosulfonation of
N-phenyl-Nꢁ-2-pyridylurea.
The acid-catalyzed ring-opening reaction of 2,3,6-triphenyl-2,3-
dihydro-1,3,5-thiadiazin-4-one (6) to yield N-phenyl-Nꢁ-thiobenzo-
ylurea (7) resembles the previously reported7 ring-opening of 1,
6-diphenylhexahydro-s-triazine-2,4-dione to give N-(sulfonylphenyl)-
Nꢁ-carbamoylurea by reaction with chlorosulfonic acid. The proposed
mechanism for the acid-catalysed ring-opening of 6 is given in
Scheme 3.

1934
R. J. Cremlyn et al.
SCHEME 3
Thiobenzoyl isocyanate is reported9 to react with dibenzylide-
neethylenediamine (11) to yield the bis (4 + 2) cycloadduct 12, and
the reaction was successfully repeated in xylene at room tem-
perature. On the other hand reaction at 90◦C resulted in the
formation of a ring-opened product, namely N,Nꢁ-dithiobenzoyl-
carbamoylethylenediamine (13) (Scheme 4). The latter compound was
also obtained when the cycloadduct 12 was heated with ethanolic hy-
drochloric acid, in an acid-catalyzed ring-opening directly analogous
to the conversion of 6 into 7 (Scheme 2). Reaction of the cycloadduct
12 with excess chlorosulfonic acid (10 molar equivalents) in thionyl
SCHEME 4

Chlorosulfonation
1935
chloride at room temperature did not give the expected tetrachlorosul-
fonyl derivative but instead gave the ring-opened bis-sulfonyl chloride
(14) (Scheme 4). This product gave a positive Beilstein test for chlo-
rine and sulfur, and was condensed with diethylamine to yield the di-
ethylsulfonamide (15). The mass spectra of the products 14 and 15
showed the relevant molecular ions, and the former also showed a
fragment ion corresponding to the loss of one chlorosulfonyl moiety.
Their NMR spectra showed the aromatic proton resonances as well-
defined AAꢁBBꢁ patterns, indicative of para-substitution, and the cor-
rect aliphatic:aromatic proton ratio of 1:3. The formation of the para-
substituted benzene rings in 14 suggests that chlorosulfonation of the
aromatic nuclei is occurring prior to ring-opening, namely before for-
mation of the thiocarbamoyl group, which would be expected to favor
ortho-substitution via the intermediate thiosulfonic acid, as observed
in the chlorosulfonation of 7 (Scheme 2).
Reaction of chlorosulfonyl isocyanate with benzylideneaniline gave
3,5-dichlorosulfonyl-1,6-diphenylhexahydro-s-triazine-2,4-dione (16)
as described by Suschitzky and Bentley.10 Subsequent treatment of this
disulfonyl chloride with potassium iodide gave 17, and then methyla-
tion afforded 3,5-dimethyl-1,6-diphenylhexa-hydro-s-triazine-2,4-dione
(18). The latter, by reaction with excess chlorosulfonic acid (12 molar
equivalents) in thionyl chloride at room temperature gave the dichloro-
sulfonyl derivative 19 in good yield. The use of less reagent (6 molar
equivalents) afforded only a low yield of the product. The bis-sulfonyl
chloride (19) was condensed with ethylamine, dimethylamine, and di-
ethylamine to give the corresponding sulfonamides (20–22) (Scheme 5).
The NMR spectra of the derivatives showed the aromatic proton res-
onances as a complex pattern, possibly indicative of a mixture of meta-
and para-sulfonation. Their EI mass spectra did not exhibit the molec-
ular ions but only fragment ions corresponding in each case to loss of
the relevant sulfonamido moiety. On the other hand the FAB mass spec-
trum of the diethylsulfonamide (22) showed the expected M+ + 1 ion.
In conclusion, chlorosulfonation of the aldimine-isocyanate cy-
cloadducts with chlorosulfonic acid is only successful when all the
ring nitrogen atoms are substituted, as in compounds 2 and 18. In
the other substrates (6, 12, and 17), acid-catalyzed ring-opening oc-
curs, so the products are the chlorosulfonyl derivatives of the corre-
sponding open-chain compounds. This is supported by the observation
that 1,6-diphenylhexahydro-s-triazine-2,4-dione (17) is known7 to re-
act with chlorosulfonic acid to give N-(para-chlorosulfonylphenyl)-Nꢁ-
carbamoylurea by an acid-catalyzed ring-opening reaction, whereas
the corresponding N,Nꢁ-dimethyl derivative (18) formed the bis-sulfonyl
chloride derivative (19) without ring-opening.

1936
R. J. Cremlyn et al.
SCHEME 5
EXPERIMENTAL
Melting points were determined with a Gallenkamp electric apparatus
and are uncorrected. IR spectra were recorded as nujol mulls using
a Perkin Elmer 237 spectrophotometer. NMR spectra were measured
with a Bruker AC 250 spectrometer and tetramethylsilane as internal
standard and DMSO-d6 as solvent, unless otherwise stated. Reso-
nances reduced by D2O treatment are indicated by an asterisk. EI
mass spectra were obtained using a VG Micromass 16F spectrometer
operating at 70 eV.
1,4-Diphenyldiazetidin-2-one (1)
Benzylideneaniline (10 g, 0.006 mmol) and sodium cyanate (5.38 g,
0.10 mmol) were added to glacial acetic acid (30 ml) and the mixture
was stirred at 0◦C for 2 h. The solvent was evaporated off under vac-
uum and the resultant solid was washed with ice-water and dried to
give 1 (8.41 g, 68%), m.p. 224–225◦C. (Found: C, 74.6; H, 5.7; N, 12.8.
C14H12N2O requires C, 74.9; H, 5.4; N, 12.5%). IR: vmax 3300 (NH), 1650
(C O); 1600 (ArC C) cm−1 1H NMR: ∂9.0∗ (br s, 1H, NH), 7.4–7.1
.

Chlorosulfonation
1937
(m, 10H, ArH), 6.7 (s, 1H, CH). 13C NMR: ∂168 (C O), 154 (CH), 128–
117 (Ar). MS: 224 (M+).
1,4-Diphenyl-3-methyldiazetidin-2-one (2)
The diphenyldiazetidinone (1) (5 g, 0.02 mmol) gradually was added to
a stirred solution of sodium hydride (2 g) in dry DMF (20 ml) at room
temperature. The mixture was heated on a water bath until a clear
solution was obtained. Methyl iodide (3.76 g) was added with stirring
and after 1 h the mixture was poured into water. The resultant solid was
filtered off under suction and was recrystallized from ethanol to yield
the N-methyl derivative (2) (1.3 g, 27%), m, p. 220–222◦C. IR: vmax1650
1
(C O), 1600 (ArC C) cm−1. H NMR: ∂7.4–7.2 (m, 10H, ArH), 6.9 (s,
1H, CH), 1.7 (s, 3H, Me). MS: 238 (M+).
Chlorosulfonation of 1,4-Diphenyl-3-methyldiazetidin-2-
one (2)
The phenylmethyldiazetidinone (2) (2.38 g, 0.01 mmol) gradally was
added to a solution of chlorosulfonic acid (3.5 g, 0.03 mmol) in excess
thionyl chloride (20 ml). The mixture was warmed on the water bath
(50◦C) for 3 h and poured onto ice-water (100 ml), with stirring. The
resultant solid was filtered off and dried in vacuo to yield the disulfonyl
chloride (3) (1.6 g, 37%), m.p. 180–182◦C. The product showed positive
Beilstein tests for Cl and S. IR: vmax 1650 (C O), 1360, 1180 (SO2) cm−1
.
1H NMR: ∂8.1–7.75 (m, 8H, ArH, AAꢁBBꢁ patterns), 6.8 (s, 1H, CH), 1.7
(s, 3H, Me). MS: 435 (M+).
Condensation of (3) with (a) Dimethylamine
A solution of the bis-sulfonyl chloride (3) (2.2 g, 0.005 mmol) in cold ace-
tone (20 ml) was reacted with excess dimethylamine (1.8 g, 0.04 mmol)
at room temperature (for 8 h). The mixture was added to ice-water
(100 ml): The solid precipitate was filtered off under vacuum and re-
crystallized from methanol to give the dimethylsulfonamide 4 (1.7 g,
70%), m.p. 215–217◦C. IR: vmax1650 (C O) 1600 (ArC C), 1365, 1180
1
(SO2) cm−1. H NMR: ∂8.0–7.6 (m, 8H, ArH, AAꢁBBꢁ patterns), 2.9 (s,
12H, NMe2), 1.8 (s, 3H, N Me). MS: 484 (M+).
Condensation of (3) with (b) Diethylamine
Treatment with excess amine similarly gave the corresponding diethyl-
sulfonamide (5) (74%), m.p. 220–222◦C. (Found: C, 56.5; H, 6.1; N, 10.5.

1938
R. J. Cremlyn et al.
C23H34N4O5S2 requires C, 56.7; H, 6.3; N, 10.4%). IR: vmax 1650 (C O),
1600 (ArC C), 1370, 1180 (SO2) cm−1. 1H NMR: ∂7.9–7.5 (m, 8H, ArH,
AAꢁBBꢁ patterns), 3.3 (q, 8H, NCH2Me), 1.8 (s, 3H, NMe), 1.2 (t, 12H,
NCH2Me). MS: 540 (M+).
2,3,6-Triphenyl-2,3-dihydro-1,3,5-thiadiazin-4-one (6)
A mixture of 2-phenylthiazoline-4,5-dione (2.0 g, 0.012 mmol) and ben-
zylideneaniline (2.2 g, 0.012 mmol) was added to xylene (25 ml). The
solution was stirred at room temperature (15 min), heated on the water
bath (30 min) and cooled (0◦C). The resultant precipitate was filtered off
under suction and washed with ice-cold ethanol to give the cycloadduct
6 (2.18 g, 54%), m.p. 188–190◦C (lit,9 193–194◦C). (Found: C, 73.3; H,
4.7; N, 8.1. C21H16 N2OS requires C, 73.2; H, 4.6; N, 8.1%). IR: vmax 1660
(C O), cm−1. 1H NMR ∂7.9–7.2 (m, 15H, ArH), 6.8 (s, 1H, CH). FAB (+)
MS: 345 (M+ + 1).
Reaction of the Cycloadduct 6 with Chlorosulfonic Acid
2,3,6-Triphenyl-2,3-dihydro-1,3,5-thiadiazin-4-one (6) (5 g, 0.014 mmol)
was added gradually to a cold solution of chlorosulfonic acid (13 g,
0.112 mmol) in thionyl chloride (20 ml). The mixture was left at room
temperature for 3 days and was poured onto ice-water (200 g). The solid
precipitate was collected, washed with water, and dried in vacuo to give
the sulfonyl chlorides 8 and 9 (3.2 g, 48%), m.p. 155–157◦C. IR: vmax
3300 (NH), 1660 (C O) cm−1. 1H NMR: ∂9.8∗ (br, s, SO3H), 9.0∗ (s, 2H,
NH), 7.9–7.6 (m, 8H, ArH).
The bis-Diethylsulfonamide Derivative 10
The mixture of the sulfonyl chlorides (8 and 9) (2 g) was reacted with
excess diethylamine in ethanol (20 ml) at room temperature (3 h). The
reaction mixture was added to ice-water (100 ml) and the solid was fil-
tered off under suction, washed with icewater, and recrystallized twice
from ethanol to give the diethyl-sulfonamide 10 (13 g, 56%), m.p. 181–
182◦C. Found: C, 50. 4; H, 5.6; N, 10.4. C22H30N4O5S requires C, 50.
2; H, 5.7; N, 10.6%). IR: vmax3300 (NH), 1660 (C O), 1360, 1180 (SO2)
1
cm−1. H NMR: ∂11.8∗, 11.1∗ (2xbr s, 2H, NH), 8.1–7.6 (m, 8H, ArH),
3.0, 2.7 (2xq, 8H, CH2Me), 1.1, 1.0 (2xt, 12H, CH2Me). MS: 526 (M+).
N-Phenyl-Nꢀ-thiobenzoylurea (7)
2,3,6-Triphenyl-2,3-dihydro-1,3,5-thiadiazin-4-one (6) (2 g) was heated
on a water-bath with concentrated hydrochloric acid (5 ml) in methanol
(20 ml) for 30 min. The clear yellow solution was evaporated under

Chlorosulfonation
1939
reduced pressure and the solid residue was washed with ether to give
the thiobenzoylurea (7) (0.43 g, 27%). (Found: C, 65. 4; H, 4.5; N, 10.6.
C14H12N2OS requires C, 65.6; H, 4.7; N, 10.9%). 1H NMR: ∂10.8∗, 10.1∗
(2xbr s, 2H, NH), 8.1–7.6 (m, 10H, ArH). MS: 256 (M+). Evaporation
of the ether washings gave a residue of benzaldehyde, identified by
formation of the 2,4-dinitrophenyl-hydrazone derivative.
Reaction of Dibenzylideneethylenediamine (11)
with Thiobenzoyl Isocyanate
(a) At Room Temperature
A solution of dibenzylideneethylenediamine (11) (2 g, 0.0085 mmol)
and thiobenzoyl isocyanate (3.1 g, 0.02 mmol) in xylene (30 ml) was
stirred at room temperature (1 h). The solid precipitate was filtered off
with suction, washed with ether, and dried to give the cycloadduct 12
(3.2 g, 67%), m.p. 228–230◦C (lit.9 230–231◦C). (Found: C, 68.5; H, 4.4;
N, 9.6. C32H26N4O2S2 requires C, 68. 3; H, 4.6; N 9.9%). IR: vmax 1670
1
(C O), 1620 (C N), 1600 (ArC C) cm−1. H NMR: ∂7.9–7.0 (m, 20H,
ArH), 6.9 (s, 2H, CHN), 3.0–2.9 (q, 4H, CH2). FAB (+) MS: 563 (M+ + 1).
(b) At 90◦C
Repetition of the reaction of dibenzylideneethylenediamine and
thiobenzoyl isocyanate (2.3 equivalents) in xylene at 90◦C (1 h) afforded
N,Nꢁ-di (thiobenzoylcarbamoyl) ethylenediamine (13) (0.8 g, 54%), m.p.
238–240◦C. (Found: C, 55.6; H, 4.4; N, 14.5. C18H18N4O2S2 requires C,
55.9; H, 4.7; N, 14.5%). IR: vmax 3200 (NH), 1660 (C O) cm−1. 1H NMR
(CDCl3): ∂10.0∗, 9.5∗ (2xbr s, 2H, NH), 8.1–7.4 (m, 10H, ArH), 3.88 (br
t, 4H, CH2). MS: 386 (M+).
Reaction of the Cycloadduct 12 with Chlorosulfonic Acid
The cycloadduct 12 (5.0 g, 0.0122 mmol) was reacted with chlorosul-
fonic acid in thionyl chloride (20 ml) at room temperature (3 days). The
solution was added to crushed ice (100 g) and the solid precipitate was
filtered off under suction, washed with cold water, and dried in a vac-
uum desiccator to give the bis-sulfonyl chloride (14), (3.4 g, 44%), m.p.
147–150◦C. IR: vmax 3300, 1160 (SO2) cm−1. 1H NMR: ∂10.6∗, 9.2∗ (2xbr
s, 4H, NH), 8.1–7.0 (m, 8H, ArH), 3.9 (t, 4H, CH2). MS: 522, 518 (M+).
The Diethylsulfonamide Derivative (15)
Condensation of the bis-sulfonyl chloride (14) with excess diethylamine
(7 molar equivalents) in methanol at room temperature, addition of

1940
R. J. Cremlyn et al.
ice-water, and recrystallization from ethanol, afforded the diethylsul-
fonamide 15 (1.64 g, 72%), m.p. 80–82◦C. (Found: C, 47.2; H, 5.4; N, 12.6.
1
C26H36N6O6S4 requires C, 47.5; H, 5.5; N, 12.8%). H NMR: ∂10.3∗,
9.7∗ (2xbr, s 4H, NH), 7.9–7.2 (M, 8H, ArH, AAꢁBBꢁ pattern), 3.8 (t,
4H, CH2CH2), 3.0–2.7 (q, 8H, NCH2Me), 1.0 (t, 12H, NCH2Me) MS:
656 (M+).
3,5-Dimethyl-1,6-diphenylhexahydro-s-triazine-2,4-dione
(18)
Benzylideneaniline was reacted with chlorosulfonyl isocyanate as
previously described10 to give 3,5-dichlorosulfonyl-1,6-diphenyl hexa-
hydro-s-triazine-2,4-dione (16). The cycloadduct, by treatment with
aqueous potassium iodide, gave 1,6-diphenylhexahydro-s-triazine-2,4-
dione (17), and subsequent methylation (methyl iodide-sodium hydride
in DMF) afforded the dimethyl derivative (18) (58%), m.p. 114–115◦C
(lit.10 112◦C). (Found: C, 69.1; H, 5.6; N, 14.0. C17H17N3O2 requires
1
C, 69.1; H, 5.7; N, 14.2%). IR: vmax 1680, 1670(C O) cm−1. H NMR
(CDCl3): ∂7.4–7.1 (m, 10H, ArH), 6.1 (s, 1H, CH), 3.0, 2.9 (2xs, 6H, Me).
MS: 295 (M+).
Chlorosulfonation of 18
3,5-Dimethyl-1,6-diphenylhexahydro-s-triazine-2,4-dione (18) (5 g,
0.018 mmol) was added portionwise to a cold solution of chlorosulfonic
acid (26 g, 0.23 mmol) in thionyl chloride (20 ml). The mixture was left
at room temperature for 3 days, poured onto ice-water, and the solid pre-
cipitate collected, washed with water and dried in a vacuum desiccator
(P2O5) to give the bis-sulfonyl chloride (19) (5.8 g, 65%), m.p. 82–8◦C.
IR: vmax1680, 1670 (C O), 1340, 1160 (SO2) cm−1. MS: 393 (M+-SO2Cl).
The bis-Ethylsulfonamide (20)
Prepared using ethylamine (5 molar equivalents): 73%, m.p. 86–89◦C.
(Found: C, 49.1; H, 5.2; N, 13.5. C21H27N5O6S2 requires C, 49.5; H, 5.3;
N, 13.7%). 1H NMR: ∂10.1∗ (br s, 2H, NHEt), 7.7–7.1 (m, 8H, ArH), 6.1
(s, 1H, CH), 2.7–2.5 (q, 4H, NCH2Me), 1.1–1.0 (t, 6H, NCH2Me). MS:
402 (M+-SO2NH-Et).
The bis-Dimethylsulfonamide (21)
Prepared using dimethylamine: (59%), m.p. 88–90◦C. (Found: C, 49.4;
H, 5.1; N, 13.6. C21H27N5O6S2 requires C, 49.5; H, 5.3; N, 13.7%).

Chlorosulfonation
1941
1H NMR: ∂7.8–7.1 (m, 8H, ArH), 6.1 (s, 1H, CH), 3.1, 3.2 (2xs, 12H,
NMe2). MS 402 (M+-SO2NMe2).
The bis-Diethylsulfonamide (22)
Prepared using diethylamine: (68%), m.p. 91–93◦C. (Found: C, 53.2; H,
6.2; N, 12.2. C25H35N5O6S2 requires C, 53.1; H, 6.2; N, 12.4%). 1H NMR:
∂7.7–7.2 (m, 8H, ArH), 6.3 (s, 1H, CH), 3.36, 3.37, (2xq, 8H, NCH2Me),
1.1–1.0 (t, 12H, NCH2Me). MS: 430 (M+-SO2NEt2). FAB(+) MS: 566
(M+ + 1).
REFERENCES
[1] R. J. Cremlyn, Chlorosulfonic Acid: A Versatile Reagent (Royal Society of Chemistry,
Cambridge, 2002).
[2] R. J. Cremlyn, J. P. Bassin, S. Farouk, M. Potterton, and T. Mattu, Phosphorus,
Sulfur, and Silicon, 73, 107 (1992).
[3] R. J. Cremlyn, R. M. Ellam, S. Farouk, S. Graham, and A. Williams, Phosphorus,
Sulfur, and Silicon, 122, 87 (1997).
[4] R. J. Cremlyn, R. M. Ellam, and S. Farouk, Phosphorus, Sulfur, and Silicon, 161,
213 (2000).
[5] S. Farouk, Ph.D. Thesis, University of Hertfordshire, (1994), p. 28.
[6] N. A. Lange, J. Amer. Chem. Soc., 48, 2440 (1926).
[7] R. J. Cremlyn, R. M. Ellam, and S. Farouk, Pesticide Science, 52, 70 (1998).
[8] N. V. Badami, R. J. Cremlyn, and F. J. Swinbourne, Aust. J. Chem., 30, 1793 (1973).
[9] O. Tsuge and S. Kanema, Bull. Chem. Soc. Jpn., 45, 2877 (1972).
[10] H. Suschitzky and R. L. Bentley, J. Chem. Soc. Perkin, 1, 1725 (1976).