One - Pot synthesis of novel sulfur and selenium heterocycles by directed ortho-lithiation

Article abstract of DOI:10.1002/jhet.5570380330

A procedure for the synthesis of benzo[e][1,3]thiazine-2,4-diones from benzamides by directed lithiation and sequential treatment with sulfur and phosgene is reported. Use of thiophosgene afforded 2-thioxo-2,3-dihydro-benzo[e][1,3]thiazin-4-ones. Application of this methodology to benzenesulfonamides afforded the previously unknown 1,1-dioxo-1,2-dihydro-1,4-dithia-2-aza-naphthalen-3-one ring system with phosgene and the 1,2-dioxo-2-phenyl-2,3-dihydrobenzo[e][1,4,2]dithiazine-3-one ring system with thiophosgene. Use of selenium in place of sulfur afforded the novel analogous selenium heterocycles, however in the case of benzamides the use of selenium and phosgene afforded benzo[d]isoselenazol-3-ones unexpectedly.

Full text of DOI:10.1002/jhet.5570380330

May-Jun 2001
One - Pot Synthesis of Novel Sulfur and Selenium Heterocycles
by Directed ortho-Lithiation
723
S. W. Wright
Pfizer Global Research and Development, Groton, CT 06340
Received October 23, 2000
A procedure for the synthesis of benzo[e][1,3]thiazine-2,4-diones from benzamides by directed lithiation
and sequential treatment with sulfur and phosgene is reported. Use of thiophosgene afforded 2-thioxo-2,3-
dihydro-benzo[e][1,3]thiazin-4-ones. Application of this methodology to benzenesulfonamides afforded the
previously unknown 1,1-dioxo-1,2-dihydro-1,4-dithia-2-aza-naphthalen-3-one ring system with phosgene
and the 1,2-dioxo-2-phenyl-2,3-dihydrobenzo[e][1,4,2]dithiazine-3-one ring system with thiophosgene.
Use of selenium in place of sulfur afforded the novel analogous selenium heterocycles, however in the case
of benzamides the use of selenium and phosgene afforded benzo[d]isoselenazol-3-ones unexpectedly.
J. Heterocyclic Chem., 38, 723 (2001).
Directed ortho-metalation methodology offers a pre-
benzo[e][1,3]selenazine-2,4-dione ring system (4). An
examination of the literature revealed that these ring sys-
tems are relatively obscure. Benzo[e][1,3]thiazine-2,4-
diones have been prepared previously from methyl thiosal-
icylate by reaction with an isocyanate, or by the reaction of
a benzo[d]isothiazol-3-one with phosgene, followed by
subsequent reaction with a substituted formamide and acid
hydrolysis [6]. Alternatively, benzo[e][1,3]thiazine-2,4-
diones have been prepared by the reaction of a thiosali-
cylic acid amide with phosgene [7]. The few benzo[e]-
[1,3]selenazine-2,4-diones that have been reported were
prepared by more circuitous routes, for example by the
reaction of 2-(benzylseleno)-N-trimethylsilyl benzanilide
with phosgene and by the ring expansion of a benzo[d]-
isoselenazol-3-one [8].
dictable and widely applicable synthetic strategy for the
regiospecific construction of substituted aromatic com-
pounds [1]. This methodology has previously been used
for the construction of heterocyclic systems containing
sulfur and selenium, such as benzo[d]isoselenazol-3-one 1
and benzo[d]isothiazol-3-ones 2 (Figure 1) [2]. These ring
systems have been of biological interest as anti-inflamma-
tory agents and as inhibitors of matrix metalloproteases
[3]. Ebselen (1a) is a particularly well known selenium
heterocycle that has been the subject of extensive study as
a small molecule mimic of the enzyme glutathione peroxi-
dase (GPx) [4]. Many analogs of Ebselen, incorporating a
variety of selenium heterocycles, have been prepared and
studied for the treatment of diseases in which reactive oxy-
gen species are thought to play a role [5].
We sought a more general approach that would proceed in
a minimum number of synthetic steps from readily available
commercial starting materials with a broad range of potential
substituents, and which would avoid the need to isolate and
perform synthetic manipulations upon sensitive thiosalicylic
acid derivatives or their selenium counterparts. Our attention
turned quickly to the use of directed metalation, which would
allow the functionalization of a wide range of readily pre-
pared benzamides in an operationally simple and regiochem-
ically predictable manner. This would allow the efficient
preparation of analogs of known ring systems, such as 3 and
4. We were further attracted by the possibility that this
methodology would allow access to entirely unknown
heterocyclic systems, for example 1,1-dioxo-2,3-dihydro-
benzo[e][1,4,2]dithiazine-3-one 5 and 1,1-dioxo-2,3-
dihydrobenzo[e][1,4,2]thiaselenazine-3-one 6. The possibil-
ity of carrying out the entire reaction sequence, from directed
metalation through to the final heterocyclic product in one
reaction flask was also attractive, despite the variety of
potential difficulties that can be encountered in attempting to
carry out multiple synthetic steps in a one - pot manner. We
anticipated that the reaction of the dilithiated benzamide with
sulfur or selenium would afford the corresponding chalco-
genide/amide dianion, which should cyclize upon treatment
with a suitable bifunctional electrophile (Scheme 1).
We sought to prepare related sulfur and selenium con-
taining heterocyclic compounds which might have similar
biological properties, in which the chalcogen atom was
incorporated in a six - membered ring, for example the
benzo[e][1,3]thiazine-2,4-dione ring system (3) and the

724
S. W. Wright
Vol. 38
Tellurium was introduced successfully using the directed
metalation strategy, as evidenced by trapping the interme-
diate tellurobenzamide dianion with iodomethane [9].
Subsequent derivatization with phosgene afforded
intractable mixtures of unidentified products as well as a
precipitate of black tellurium. The methodology was
extended successfully to benzenesulfonamides to afford
products 5, 6, 9, and 10. The method was not of prepara-
tive value when thiobenzamides were employed as sub-
strates for the directed ortho-metalation. These afforded
complex mixtures of products, in which relatively small
amounts (< 20%) of the desired heterocyclic targets
(Figure 2) were present.
In a typical experiment, the benzamide derivative was
treated with 2 equivalents of n-butyllithium in tetrahydro-
furane (THF) at 0 °C for 1 hour, after which 1 equivalent
of sulfur or selenium powder was added. The reaction
mixture was heated at 50 °C until the starting amide was
Table 1
Substrate
Benzanilide
Product
3a
3b
5a
5b
6a
6b
7a
7b
8a
8b
9a
9b
10a
10b
X
S
S
S
S
Se
Se
S
Y
O
O
O
O
O
O
S
S
S
S
S
R
Ph
Me
Ph
Me
Ph
Me
Ph
Me
Ph
Me
Ph
Me
Ph
Z
CO
CO
Yield [a]
56%
74%
80%
72%
69%
62%
65%
78%
66%
72%
70%
69%
57%
90%
mp, °C
144 - 146 [b]
122 - 124 [c]
164 – 166
101 – 103
152 – 154
96 - 97
157 - 159 [d]
142 - 143 [e]
156 - 157
145 - 147
175 - 177
140 - 142
192 - 193
129 – 131
N-Methylbenzamide
Benzenesulfonanilide
N-Methylbenzenesulfonamide
Benzenesulfonanilide
N-Methylbenzenesulfonamide
Benzanilide
SO
SO
SO
SO
CO
CO
CO
CO
SO
SO
SO
SO
2
2
2
2
N-Methylbenzamide
Benzanilide
S
Se
Se
S
S
Se
Se
N-Methylbenzamide
Benzenesulfonanilide
N-Methylbenzenesulfonamide
Benzenesulfonanilide
N-Methylbenzenesulfonamide
2
2
2
2
S
S
S
Me
[a] All yields refer to analytically pure products; [b] lit. mp. 145 – 146 °C: H. Boeshagen, W. Geiger, H. Hulpke and C. Wunsche, Chem. Ber. 104, 3757
(1971); [c] lit. mp. 119 – 121 °C: H. Boeshagen, W. Geiger, H. Hulpke and C. Wunsche, Chem. Ber. 104, 3757 (1971); [d] lit. mp. 155 – 157 °C: G.
Wagner and P. Richter, Pharmazie, 22, 611 (1967); [e] lit. mp. 144 – 146
°C: G. Wagner and P. Richter, Pharmazie, 22, 611 (1967).
consumed as judged by tlc analysis of aliquots removed
and quenched into dilute acetic acid. The mixture was
then cooled thoroughly in ice and 1 equivalent of phosgene
dissolved in toluene was added. The reaction mixture was
stirred overnight at ambient temperature prior to extractive
workup. Crude products were in most cases > 70% pure
1
by H NMR analysis. Purification was readily effected in
most cases by recrystallization. In certain cases chro-
matography proved to be more effective due to high solu-
bility of the product in the usual recrystallization solvents.
The reaction proved to be generally successful for most
of the combinations of substrate benzamide and chalcogen
(sulfur or selenium) that were examined (Table 1). The
directed ortho-lithiation and subsequent reaction with sul-
fur or selenium was uneventful, providing the desired
2-mercapto or 2-seleno benzamide intermediate with little
or no by-product formation as judged by tlc analysis.
The cyclization of the intermediate 2-thio- or 2-seleno-
benzamide to the target heterocycle was found to require
the use of a very reactive electrophile. Other synthetic
equivalents to phosgene, such as ethyl chloroformate, 1,1'-
carbonyldiimidazole, and dimethyl carbonate, were tried
without success. Thiophosgene was found to react equally
well as phosgene. As anticipated, the use of thionyl chlo-
ride or sulfuryl chloride in place of phosgene did not afford
a new six-membered heterocycle, but instead served to
oxidize the intermediate 2-selenobenzamide or 2-thioben-
zamide dianion to the corresponding benzo[d]isoselena-

May-Jun 2001
One - Pot Synthesis of Novel Sulfur and Selenium Heterocycles
725
Anal. Calcd. for C H NO S: C, 65.87; H, 3.55; N, 5.49.
Found: C, 65.83; H, 3.51; N, 5.35.
zol-3-ones 1 and benzo[d]isothiazol-3-ones 2. However, the
reaction of phosgene with the intermediate 2-selenobenza-
mide dianion also afforded the corresponding benzo[d]-
isoselenazol-3-ones 1 in high yield. This unexpected result
was confirmed by combustion analysis and comparison of
spectroscopic data and melting points for these products
with those of authentic samples of 1a and 1b.
14
9
2
3-Methylbenzo[e][1,3]thiazine-2,4-dione (3b).
This compound was obtained in 74% yield from N-methylben-
zamide as light tan crystals following recrystallization from
1
toluene - hexane, mp 122 – 124 °C. H NMR (deuteriochloro-
form): δ 8.37 (d, J = 7.9 Hz, 1 H), 7.58 (d of d, J = 7.9, 8.3 Hz, 1
H), 7.42 (d of d, J = 7.9, 8.3 Hz, 1 H), 7.28 (d, J = 7.9 Hz, 1 H),
+
3.51 (s, 3 H); ms: (EI) m/z = 193 (M ).
EXPERIMENTAL
Anal. Calcd. for C H NO S: C, 55.95; H, 3.65; N, 7.25.
9
7
2
Found: C, 56.22; H, 3.70; N, 7.08.
All reactions were carried out under an atmosphere of dry
nitrogen. The starting materials listed in Table 1 were commer-
cial reagents and were used as received without additional purifi-
cation. Sublimed sulfur powder meeting USP specifications
(Fisher S594) and 100 mesh selenium powder (Aldrich 20,965-1)
were used. Phosgene solution (20% in toluene, ca. 1.9 M) was
obtained from Fluka. Commercial anhydrous grade solvents were
used without further drying. All solutions were dried over anhy-
drous magnesium sulfate prior to evaporation on a rotary evapo-
rator at ca. 30 Torr. Chromatography was performed using a
Biotage Flash 40 pressure chromatography apparatus fitted with
a 40S silica gel cartridge. Melting points were determined on a
Thomas Hoover melting point apparatus and are uncorrected.
NMR spectra were recorded on Varian Unity Inova 400 spec-
trometers. Mass spectra were recorded on a Hewlett Packard
Model 5989 mass spectrometer using chemical ionization with
ammonia. Elemental analyses were performed by Schwarzkopf
Microanalytical Laboratory, Woodside, New York, USA.
1,1-Dioxo-2-phenyl-2,3-dihydrobenzo[e][1,4,2]dithiazine-3-one
(5a).
This compound was obtained in 80% yield from benzenesulfo-
nanilide as white crystals following recrystallization from
1-chlorobutane, mp 164 – 166 °C. H NMR (deuteriochloro-
form): δ 8.08 (d, J = 8.0 Hz, 1 H), 7.73 (m, 1 H), 7.58 (m, 2 H),
7.49 (m, 3 H), 7.32 (m, 2 H); ms: (NH CI) m/z = 292 (MH ).
1
+
3
Anal. Calcd. for C H NO S : C, 53.59; H, 3.11; N, 4.81.
13
9
3 2
Found: C, 53.41; H, 2.97; N, 4.67.
1,1-Dioxo-2-methyl-2,3-dihydrobenzo[e][1,4,2]dithiazine-3-one
(5b).
This compound was obtained in 72% yield from N-methylben-
zenesulfonamide as white crystals following trituration with
diethyl ether - acetone, mp 101 – 103 °C. H NMR (deuteriochlo-
roform): δ 8.01 (d, J = 8.0 Hz, 1 H), 7.63 (d of d, J = 8.0, 7.7 Hz,
1 H), 7.51 (d of d, J = 8.0, 7.7 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 1 H),
3.39 (s, 3 H); ms: (EI) m/z = 229 (M ).
1
+
General Procedure for the Preparation of Sulfur and Selenium
Heterocycles.
Anal. Calcd. for C H NO S : C, 41.91; H, 3.08; N, 6.11.
8
7
3 2
Found: C, 42.10; H, 3.18; N, 6.02.
To a stirred solution of the appropriate benzamide or benzene-
sulfonamide (6.25 mmol) in 40 mL of dry THF was added
n-butyllithium (5 mL of a 2.5 M solution in hexanes, 12.5 mmol)
with cooling in a Dry Ice - acetone bath. Upon completion of the
addition, the bath was removed and the mixture was allowed to
warm spontaneously to 0 °C. The mixture was then stirred in an
ice bath for 1 hour before the addition of sulfur (0.200 g, 6.25
mmol) or selenium (0.492 g, 6.25 mmol). The ice bath was
removed and the mixture was stirred for 1 hour at 50 °C, or until
all of the element had dissolved and tlc analysis of an aliquot
quenched with 1 M aqueous acetic acid indicated that the starting
benzamide had been consumed. The reaction flask was then
cooled in ice for 30 minutes, after which phosgene (3.4 mL of a
1.9 M solution in toluene, 6.25 mmol) or thiophosgene (0.48 mL,
6.25 mmol) was added. The ice bath was removed and the mix-
ture was stirred for 18 hours at 20 °C before being poured into
water (75 mL) and ethyl acetate (75 mL). The mixture was
stirred for 10 minutes, separated, and the ethyl acetate phase was
washed with water, twice with brine, dried, and concentrated to
afford the crude product, which was purified by silica gel chro-
matography using 5:1 hexanes - ethyl acetate to elute the column
or by recrystallization from the indicated solvent(s).
1,1-Dioxo-2-phenyl- 2,3-dihydrobenzo[e][1,4,2]thiaselenazine-
3-one (6a).
This compound was obtained in 69% yield from benzenesulfo-
nanilide as white crystals following recrystallization from
1
1-chlorobutane:hexane, mp 152 – 154 °C. H NMR (deuteriochlo-
roform): δ 8.14 (d, J = 8.0 Hz, 1 H), 7.66 (m, 2H), 7.54 (m, 1 H),
+
7.47 (m, 3 H), 7.28 (m, 2 H); ms: (NH CI) m/z = 340 (MH ).
3
Anal. Calcd. for C H NO SSe: C, 46.16; H, 2.68; N, 4.14.
13
9
3
Found: C, 46.58; H, 2.67; N, 4.11.
2-Methyl-1,1-dioxo-1,2-2,3-dihydrobenzo[e][1,4,2]thiasele-
nazine -3-one (6b).
This compound was obtained in 62% yield from N-methylben-
zenesulfonamide as white crystals following chromatography on
1
silica gel, mp 96 – 97 °C. H NMR (deuteriochloroform): δ 8.05
(d, J = 7.9 Hz, 1 H), 7.59 (m, 2 H), 7.50 (d of d, J = 7.9 Hz, 6.9
+
Hz, 1 H), 3.40 (s, 3 H); ms: (EI) m/z = 277 (M ).
Anal. Calcd. for C H NO SSe: C, 34.79; H, 2.55; N, 5.07.
8
7
3
Found: C, 34.98; H, 2.59; N, 5.09.
3-Phenyl-2-thioxo-2,3-dihydrobenzo[e][1,3]thiazine-4-one (7a).
This compound was obtained in 65% yield from benzanilide as
pale yellow crystals following recrystallization from 1-chloro-
3-Phenyl-benzo[e][1,3]thiazine-2,4-dione (3a).
1
This compound was obtained in 56% yield from benzanilide as
colorless crystals following recrystallization from 1-chlorobu-
butane, mp 157 – 159 °C. H NMR (deuteriochloroform): δ 8.37
(d, J = 7.9 Hz, 1 H), 7.63 (m, 1 H); 7.56 (m, 4 H); 7.22 (m, 3 H);
1
+
tane, mp 144 – 146 °C. H NMR (deuteriochloroform): δ 8.39 (d,
ms: (NH CI) m/z = 272 (MH ).
3
J = 8.0 Hz, 1 H), 7.64 (m, 1 H); 7.51 (m, 4 H); 7.38 (m, 1 H);
Anal. Calcd. for C H NOS : C, 61.97; H, 3.34; N, 5.16.
14 9 2
+
7.22 (m, 2 H); ms: (NH CI) m/z = 256 (MH ).
Found: C, 61.97; H, 3.26; N, 5.11.
3

726
S. W. Wright
Vol. 38
3-Methyl-2-thioxo-2,3-dihydrobenzo[e][1,3]thiazine-4-one (7b).
1,1-Dioxo-2-phenyl-2,3-dihydrobenzo[e][1,4,2]thiaselenazine-3-
thione (10a).
This compound was obtained in 78% yield from N-methylben-
zamide as off - white crystals following recrystallization from
acetic acid - water, mp 142 – 143 °C. H NMR (deuteriochloro-
This compound was obtained in 57% yield from benzenesulfo-
nanilide as yellow crystals following recrystallization from
1
1
form): δ 8.33 (d, J = 8.1 Hz, 1 H), 7.59 (d of d, J = 8.1, 7.9 Hz,
toluene, mp 192 – 193 °C. H NMR (deuteriochloroform): δ 8.07
1 H), 7.43 (d of d, J = 8.1, 7.9 Hz, 1 H), 7.18 (d, J = 7.9 Hz, 1 H);
(d, J = 7.9 Hz, 1 H), 7.68 (m, 1 H), 7.62 (m, 1 H), 7.54 (m, 1 H),
+
+
ms: (EI) m/z = 209 (M ).
7.48 (m, 3 H), 7.25 (m, 2 H); ms: (EI) m/z = 355 (M ).
Anal. Calcd. for C H NOS : C, 51.65; H, 3.37; N, 6.69.
Anal. Calcd. for C H NO S Se: C, 44.07; H, 2.56; N, 3.95.
9
7
2
13 9 2 2
Found: C, 51.49; H, 3.31; N, 6.60.
Found: C, 44.23; H, 2.57; N, 3.86.
1,1-Dioxo-2-methyl-2,3-dihydrobenzo[e][1,4,2]thiaselenazine-
3-thione (10b).
3-Phenyl-2-thioxo-2,3-dihydro-benzo[e][1,3]selenazine-4-one
(8a).
This compound was obtained in 90% yield from N-methylben-
This compound was obtained in 66% yield from benzanilide as
pale yellow crystals following recrystallization from 1-chloro-
zenesulfonamide as dark yellow crystals following chromatogra-
1
1
phy on silica gel, mp 129 – 131 °C. H NMR (deuteriochloro-
butane, mp 156 – 157 °C. H NMR (deuteriochloroform): δ 8.40
form): δ 8.06 (d, J = 7.9 Hz, 1 H), 7.62 (m, 1 H), 7.53 (m, 2 H),
(d, J = 8.1 Hz, 1 H), 7.62 – 7.41 (m, 5 H); 7.34 (d, J = 7.9 Hz,
+
+
3.74 (s, 3 H); ms: (EI) m/z = 293 (M ).
1 H), 7.19 (m, 2 H); ms: (NH CI) m/z = 320 (MH ).
3
Anal. Calcd. for C H NO S Se: C, 32.88; H, 2.41; N, 4.79.
Anal. Calcd. for C H NOSSe: C, 52.84; H, 2.85; N, 4.40.
8
7
2 2
14
9
Found: C, 33.09; H, 2.38; N, 4.73.
Found: C, 52.75; H, 3.11; N, 4.38.
3-Methyl-2-thioxo-2,3-dihydro-benzo[e][1,3]selenazine-4-one
(8b).
REFERENCES AND NOTES
This compound was obtained in 72% yield from N-methylben-
[1a] V. Snieckus, Chem. Rev., 90, 879 (1990); [b] H. W. Gschwend
and H. R. Rodriguez, Org. React., 26, 1 (1979); [c] P. Beak and V.
Snieckus, Acc. Chem. Res., 15, 306 (1982); [d] N. S. Narasimhan and R.
S. Mali, Top. Curr. Chem., 138, 63 (1987).
[2a] L. Engman and A. Hallberg, J. Org. Chem., 54, 2964 (1989);
[b] S. W. Wright, J. J. Petraitis, M. M. Abelman, D. G. Batt, L. L.
Bostrom, R. L. Corbett, C. P. Decicco, S. V. Di Meo, B. Freimark, J. V.
Giannaras, A. M. Green, J. W. Jetter, D. J. Nelson, M. J. Orwat, D. J.
Pinto, M. A. Pratta, S. R. Sherk, J. M. Williams, R. L. Magolda, and E. C.
Arner, J. Med. Chem., 37, 3071 (1994).
[3a] A. Muller, E. Cadenas, P. Graf, and H. Sies, Biochem.
Pharmacol., 33, 3235 (1984); [b] A. Wendel, M. Fausel, H. Safayhi, G.
Tiegs, and R. Otter, Biochem. Pharmacol., 33, 3241 (1984); [c] M. J.
Parnham and S. Kindt, Biochem. Pharmacol., 33, 3247 (1984); [d] Y.
Tabuchi, N. Sugiyama, T. Horiuchi, M. Furusawa, and K. Furuhama,
Eur.J.Pharmacol., 272, 195 (1995); [e] E. C. Arner, M. A. Pratta, B.
Freimark, M. Lischwe, J. M. Trzaskos, R. L. Magolda, and S. W. Wright,
Biochem. J., 318, 417 (1996).
zamide as brick - red crystals following recrystallization from
1
1-chlorobutane, mp 145 – 147 °C. H NMR (deuteriochloro-
form): δ 8.42 (d, J = 7.6 Hz, 1 H), 7.55 (d of d, J = 9.6, 7.6 Hz,
1 H), 7.42 (d of d, J = 9.6, 7.6 Hz, 1 H), 7.27 (d, J = 9.6 Hz, 1 H),
+
3.95 (s, 3 H); ms: (EI) m/z = 257 (M ).
Anal. Calcd. for C H NOSSe: C, 42.20; H, 2.75; N, 5.47.
9
7
Found: C, 42.45; H, 2.72; N, 5.30.
1,1-Dioxo-2-phenyl-2,3-dihydrobenzo[e][1,4,2]dithiazine-3-
thione (9a).
This compound was obtained in 70% yield from benzenesulfo-
nanilide as dark tan crystals following recrystallization from
1
toluene, mp 175 – 177 °C. H NMR (deuteriochloroform): δ 8.01
(d, J = 7.9 Hz, 1 H), 7.72 (m, 1 H), 7.57 (m, 1 H), 7.50 (m, 4 H),
+
7.29 (m, 2 H); ms: (EI) m/z = 307 (M ).
Anal. Calcd. for C H NO S : C, 50.79; H, 2.95; N, 4.56.
13
9
2 3
[4] For a review, see: H. Sies, Free Radical Biol. Med. 14, 313
(1993).
[5] I. Erdelmeier, C. Tailhan-Lomont, and J.-C. Yadan, J. Org.
Chem., 65, 8152 (2000).
Found: C, 50.60; H, 3.09; N, 4.30.
1,1-Dioxo-2-methyl-2,3-dihydrobenzo[e][1,4,2]dithiazine-3-
thione (9b).
[6a] L. Capuano and M. Zander, Chem. Ber. 99, 3085 (1966); [b]
H. Boeshagen, W. Geiger, H. Hulpke and C. Wunsche, Chem. Ber. 104,
3757 (1971).
[7] G. Wagner and P. Richter, Pharmazie, 22, 611 (1967).
[8a] M. C. Fong, M. J. Laws, and C. H. Schiesser, Aust. J. Chem.,
48,1221 (1995); [b]M. Mbuyi, L. Christiaens, and M. Renson, Bull. Soc.
Chim. Belg., 98, 395 (1989).
This compound was obtained in 69% yield from N-methylben-
zenesulfonamide as yellow crystals following trituration with
1
diethyl ether, mp 140 – 142 °C. H NMR (deuteriochloroform): δ
8.00 (d, J = 7.9 Hz, 1 H), 7.65 (m, 1 H), 7.53 (m, 1 H), 7.40 (d,
+
J = 7.9 Hz, 1 H), 3.71 (s, 3 H); ms: (EI) m/z = 245 (M ).
Anal. Calcd. for C H NO S : C, 39.17; H, 2.88; N, 5.71.
8
7
2 3
Found: C, 39.50; H, 3.07; N, 5.62.
[9] L. Engman and A. Hallberg, J. Org. Chem., 54, 2964 (1989).