Staudinger and retro-Staudinger reactions. The dichloro-β-lactam moiety as a useful handle for the synthesis of 4-aryl-2H-1,3-benzothiazine 1,1-dioxides

Article abstract of DOI:10.1016/j.tetlet.2010.04.051

The dichloro-β-lactam ring, obtained via Staudinger reaction of 4-aryl-2H-1,3-benzothiazines, proved to be a useful protecting strategy for the synthesis of 4-aryl-2H-1,3-benzothiazine 1,1-dioxides. After oxidation of the 1,1-dichloroazeto[2,1-c][1,3]-benzothiazin-2-ones, the thiazine ring could be recovered selectively and in good yield by treatment with base. Thus, novel 4-aryl-2H-1,3-benzothiazine 1,1-dioxides were obtained efficiently.

Full text of DOI:10.1016/j.tetlet.2010.04.051

Tetrahedron Letters 51 (2010) 3205–3207
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Tetrahedron Letters
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Staudinger and retro-Staudinger reactions. The dichloro-b-lactam moiety as
a useful handle for the synthesis of 4-aryl-2H-1,3-benzothiazine 1,1-dioxides
Lajos Fodor a,b, , Péter Csomós a,b, Antal Csámpai c, Pál Sohár c,d,
*
*
a Institute of Pharmaceutical Chemistry, University of Szeged, and Research Group of Stereochemistry of the Hungarian Academy of Sciences, H-6720, Szeged, Eötvös u. 6., Hungary
b Central Laboratory, County Hospital, H-5701 Gyula, POB 46, Hungary
c Institute of Chemistry, Eötvös Loránd University, Hungary
d Protein Modelling Research Group, Hungarian Academy of Sciences and Eötvös Loránd University, H-1518 Budapest, POB 32, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
The dichloro-b-lactam ring, obtained via Staudinger reaction of 4-aryl-2H-1,3-benzothiazines, proved to
be a useful protecting strategy for the synthesis of 4-aryl-2H-1,3-benzothiazine 1,1-dioxides. After oxida-
tion of the 1,1-dichloroazeto[2,1-c][1,3]-benzothiazin-2-ones, the thiazine ring could be recovered selec-
tively and in good yield by treatment with base. Thus, novel 4-aryl-2H-1,3-benzothiazine 1,1-dioxides
were obtained efficiently.
Received 13 January 2010
Revised 22 March 2010
Accepted 12 April 2010
Available online 18 April 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
1,3-Benzothiazine
Dichloro-b-lactam
Staudinger reaction
Oxidation
Among condensed sulfur–nitrogen heterocycles, sulfones such
as 1,4-benzothiazepine 1,1-dioxides exhibit a broad range of bio-
logical activity (antiatherosclerotic,1 antihyperlipidaemic,2 muscle
relaxation accelerator3 and antiarrhythmic effects4). The six-mem-
bered homologues, 1,4-benzothiazine 1,1-dioxides, inhibit peptide
deformylase, for example,5 while 1,2-benzothiazine 1,1-dioxides
include ‘oxicam’ drugs such as meloxicam and piroxicam.6 In con-
trast, the 1,3-benzothiazine 1,1-dioxide ring system has been pre-
pared in a few cases through ring-enlargement reactions of
substituted saccharin derivatives.7 (It is noteworthy that this
method is only suitable for the synthesis of dihydro- or 4-oxo-
1,3-benzothiazine sulfones.) This stems from the synthetic difficul-
ties encountered during conventional procedures; the oxidation of
various 1,3-benzothiazines results in a ring-contraction reaction,
providing 1,2-benzoisothiazoles as products.8
As part of a programme aimed at investigations of different con-
densed S,N-heterocycles, including b-lactam-condensed deriva-
tives,9a we wanted to devise a procedure for the preparation of
potentially pharmacologically active 2H-1,3-benzothiazine sulf-
ones 6a–c (Scheme 1).
We previously studied the reactions of monochloro-, dichloro-
and aryl-substituted b-lactam-condensed benzothiazines. Under
basic conditions, several ring-enlargement reactions occurred. Thus,
1,4-9b,c and 4,1-benzothiazepines,9d isoquinolines9e and thiazoles9e
were obtained. In the course of our present investigations, we pre-
pared angularly-condensed dichloro-b-lactams 3a–c by Staudinger
reaction10 of 4-aryl-benzothiazines 1a–c.11 Surprisingly, on treat-
ment with sodium methoxide in methanol at reflux, the latter b-lac-
tams did not display the expected reactivity (ring enlargement,9b–e
ester formation12 or chloro-methoxy exchange13). Instead, the start-
ing 1,3-benzothiazines 1a–c were recovered, almost quantitatively,
via retro-Staudinger reaction.14
This observation led us to examine the use of the dichloro-b-
lactam moiety as a protecting strategy for the synthesis of sulfones
6a–c, which we could not obtain earlier by the direct oxidation of
benzothiazines 1a–c. As an example, treatment of 6,7-dimethoxy-
1,3-benzothiazines 1a–c with peracetic acid furnished 1,2-benzo-
thiazoles 2a–c instead of the expected sulfone products 6a–c
(Scheme 1).8 For the oxidation of b-lactam-condensed 1,3-thia-
zines 3a–c, peroxyacetic acid proved to be a mild and efficient re-
agent, and azetothiazine sulfones 4a–c were obtained selectively in
good yields.15 In this oxidation reaction the dichloro-b-lactam moi-
ety protected the benzothiazine ring from undergoing ring-con-
traction. Treatment of 4a–c with a refluxing solution of sodium
methoxide provided the novel target sulfones 6a–c, most probably
via 5a–c as intermediates.14 The Staudinger reactions of 6a–c with
dichloroacetyl chloride in refluxing toluene afforded b-lactams
4a–c (Scheme 1).11
* Corresponding authors. Tel.: +36 66 463763; fax: +36 66 526539 (L.F.); tel.: +36
1 3722911; fax: +36 1 3722592 (P.S.).
The structures of the new compounds were confirmed by IR and
NMR spectroscopy.11,14,15
E-mail addresses: fodor@pandy.hu (L. Fodor), sohar@chem.elte.hu (P. Sohár).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.051

3206
L. Fodor et al. / Tetrahedron Letters 51 (2010) 3205–3207
i)
MeO
MeO
S
MeO
MeO
S
MeO
MeO
S
oxidation
ref. 8.
N
N
N
ii)
O
Cl
Cl
R
R
2a−c
R
1a−c
3a−c
iii)
oxidation
O
N
O
O
S
O
O
O
S
MeO
O
CHCl
MeO
MeO
MeO
MeO
S
MeO
MeO
ii)
ii)
N
N
O
2
Cl
Cl
4a−c
R
R
R
6a−c
5a−c
i)
a: R = H;
b: R = Cl;
c: R = Me
Scheme 1. Reagents and conditions: (i) Cl2CHCOCl, Et3N, toluene, reflux, 1 h; (ii) NaOMe, MeOH, reflux, 15 min; (iii) MeC(O)OOH, MeCOOH, rt, 1 d.
The presence of a b-lactam ring was proved by the IR frequency
(1785–1808 cmÀ1) which is higher than expected16a for condensed
azetidinones, due to the electron-withdrawing effect of the neigh-
bouring CCl2 group.
References and notes
1. Brieaddy, L. E. WO Patent 9316055, 1993; Chem. Abstr. 1994, 120, 164244.
2. (a) Brieaddy, L. E. WO Patent 9605188, 1996; Chem. Abstr. 1996, 125, 114724.;
(b) Sasahara, T.; Mohri, M. WO Patent 2004/020421, 2004; Chem. Abstr. 2004,
140, 253584.; (c) Starke, I.; Alenfalk, S.; Nordberh, M. P.; Dahlstrom, M. U. J.;
Bostrom, S. J.; Lemurell, M. A.; Wallberg, A. C. WO Patent 2004076430, 2004;
Chem. Abstr. 2004, 141, 260784.
3. Kaneko, N. WO Patent 2005105793, 2005; Chem. Abstr. 2005, 143, 452896.
4. Marks, A. R.; Landry, D. W.; Deng, S.; Cheng, Z. Z.; Lehnart, S. E. WO Patent
2007024717, 2007; Chem. Abstr. 2007, 146, 295964.
5. Cali, P.; Hjelmencrantz, A.; Naerum, L. WO Patent 2005092872, 2005; Chem.
Abstr. 2005, 143, 367310.
6. Richy, F.; Scarpignato, C.; Lanas, A.; Reginster, J.-Y. Pharmacol. Res. 2009, 60,
254.
The oxidation to sulfones (products 4 and 6) follows from the
appearance of a stretching IR band-pair due to the SO2 group at fre-
quencies in accord with literature data,16b and the significant shifts
in the 1H and 13C NMR spectra of the neighbouring methylene
group (by ꢀ20 and 27.5 ppm in the 13C NMR spectra of 4 and 6),
and of the H-6 proton (7.39–7.55 ppm) relative to the values mea-
sured for 3a,b (6.69 and 6.67 ppm). A similar shift was observed for
the C-5a resonance (from 122.8 0.1 ppm to 131.4 0.1 ppm). As a
consequence of the molecular symmetry, the CH2 resonances occur
as singlets in derivatives of type 6, and as two doublets for the
other compounds investigated.
The singlet due to the methylene protons was shifted downfield
in 4a–c relative to 3b,c (by 0.06 ppm) due to the ÀI effect of the
sulfone group in the para position, while products 6a–c exhibited
opposite shifts (by 0.20 ppm). This phenomenon can be explained
by the compensating (electron-releasing) effect of the nitrogen
atom (of electron-reservoir character) in the contiguous conju-
gated bond chain.
In summary, we have developed a new procedure for the prepa-
ration of 4-aryl-2H-1,3-benzothiazine 1,1-dioxides 6a–c. Stauding-
er reaction of the substrate 4-aryl-2H-1,3-benzothiazines 1a–c
results in efficient formation of the dichloro-b-lactam subunit which
can be removed on treatment with sodium methoxide in methanol
following oxidation. This appears to be the first report of a retro-
Staudinger reaction. To the best of our knowledge, no protecting
group is available for imines from which they can be subsequently
recovered.17 Further investigations are in progress to extend the
applicability of the dichloro-b-lactam moiety as a protecting group.
7. (a) Zinnes, H.; Comes, R. A.; Shavel, J. J. Org. Chem. 1964, 29, 2068; (b) Elghamry,
I.; Döpp, D. Tetrahedron Lett. 2001, 42, 5651; (c) Elghamry, I.; Döpp, D.; Henkel,
G. J. Heterocycl. Chem. 2007, 44, 849.
8. Szabó, J.; Szücs, E.; Fodor, L.; Katócs, Á.; Bernáth, G.; Sohár, P. Tetrahedron 1988,
44, 2985.
9. (a) Fodor, L.; Szabó, J.; Sohár, P. Tetrahedron 1981, 37, 963; (b) Fodor, L.; Szabó,
J.; Bernáth, G.; Párkányi, L.; Sohár, P. Tetrahedron Lett. 1981, 22, 5077; (c) Fodor,
}
L.; Szabó, J.; Szucs, E.; Bernáth, G.; Sohár, P.; Tamás, J. Tetrahedron 1984, 40,
4089; (d) Csomós, P.; Fodor, L.; Bernáth, G.; Sinkkonen, J.; Salminen, J.;
Wiinamäki, K.; Pihlaja, K. Tetrahedron 2008, 64, 1002; (e) Fodor, L.; Szabó, J.;
Bernáth, G.; Sohár, P.; Argay, G.; Kálmán, A.; Tamás, J. Tetrahedron 1988, 44,
7180.
10. (a) Cossío, F. P.; Arrieta, A.; Sierra, M. A. Acc. Chem. Res. 2008, 41, 925;
(b) Xu, J. Arkivoc 2009, ix, 21; (c) Fu, N.; Tidwell, T. T. Tetrahedron 2008,
64, 10465.
11. General procedure for azetobenzothiazines (3a–c and 4a–c). To a stirred solution
of the 4H-1,3-benzothiazine derivative (1a–c or 6a–c) (2.0 mmol) in anhydrous
toluene (10 ml), dichloroacetyl chloride (3.0 mmol) was added. The solution
was heated at reflux and Et3N (0.4 mL, 3.0 mmol) in anhydrous toluene (20 mL)
was added dropwise over 1 h. The reaction mixture was then cooled and
filtered and the residual triethylammonium chloride was washed with toluene.
The organic layer was washed with brine (20 mL) and dried over Na2SO4. After
evaporation, the oily residue crystallized on trituration with EtOH. Analytical
data for 3a were identical to those reported earlier.9a Compound 3b: white
crystalline powder, mp 217–219 °C (from EtOH), yield 95%. mmax (KBr disc)
1788 (
m
C@O), 1262 (
m
C–O), 866 (
c
CArH, condensed benzene ring), 780 (
cCArH,
para-disubstituted ring), 677 (CCl2) cmÀ1
.
1H NMR d (500 MHz, CDCl3): 7.45
(2H, m, H-2’,6’), 7.39 (2H, m, H-3’,5’), 7.15 (1H, s, H-9), 6.69 (1H, s, H-6), 5.00
(1H, d, J = 12.1 Hz, SCH2), 4.44 (1H, d, J = 12.1 Hz, SCH2), 3.98 (3H, s, 8-OCH3),
3.88 (3H, s, 7-OCH3) ppm; 13C NMR d (125 MHz, CDCl3): 160.4 (C@O), 150.2 (C-
7), 146.9 (C-8), 135.9 (C-4’), 135.1 (C-1’), 130.1 (C-2’), 129.1 (C-3’), 122.9 (C-5a),
122.0 (C-9a), 114.7 (C-9), 111.1 (C-6), 90.4 (C-1), 73.7 (C-9b), 38.1 (CH2) ppm.
Anal. Calcd for C18H14Cl3NO3S (430.73): C, 50.19; H, 3.28; N, 3.25; S, 7.44.
Found: C, 50.35; H, 3.52; N, 3.01; S, 7.68. Compound 3c: white crystalline
Acknowledgements
The authors express their thanks to the Hungarian Scientific Re-
search Foundation (OTKA) for financial support. We are indebted to
Mrs. E. Juhász Dinyáné for technical assistance.
powder, mp 186–188 °C (from EtOH), yield 96%. mmax (KBr disc) 1785 (mC@O),

L. Fodor et al. / Tetrahedron Letters 51 (2010) 3205–3207
3207
1253
(m
C–O), 867
(
c
CArH, condensed benzene ring), 778
(c
CArH, para-
ppm, ** reversed assignments are also possible. Anal. Calcd for C17H17NO4S
(331.39): C, 61.61; H, 5.17; N, 4.23; S, 9.68. Found: C, 61.46; H, 5.33; N, 4.01; S,
9.87.
disubstituted ring), 679 (CCl2) cmÀ1
.
1H NMR d (500 MHz, CDCl3): 7.40 (2H,
m, H-2’,6’), 7.23 (2H, m, H-3’,5’), 7.17 (1H, s, H-9), 6.67 (1H, s, H-6), 5.00 (1H, d,
J = 12.1 Hz, SCH2), 4.46 (1H, d, J = 12.1 Hz, SCH2), 3.98 (3H, s, 8-OCH3), 3.88 (3H,
s, 7-OCH3), 2.38 (3H, s, CH3) ppm; 13C NMR d (125 MHz, CDCl3): 160.5 (C@O),
150.0 (C-7), 146.7 (C-8), 139.7 (C-4’), 133.3 (C-1’), 129.6 (C-3’), 128.7 (C-2’),
122.7 (C-5a), 122.2 (C-9a), 115.0 (C-9), 110.8 (C-6), 90.6 (C-1), 74.0 (C-9b), 37.9
(CH2) ppm. Anal. Calcd for C19H17Cl2NO3S (410.31): C, 55.62; H, 4.18; N, 3.41; S,
7.82. Found: C, 55.78; H, 4.01; N, 3.63; S, 8.08. Compounds 4a–c: the analytical
data were identical to those reported.14 Yields, 4a: 97%, 4b: 95%, 4c: 88%.
12. (a) Alcaide, B.; Almendros, P.; Aragoncillo, C. Chem. Rev. 2007, 107, 4437; (b)
Alcaide, B.; Almendros, P.; Redondo, M. Chem. Commun. 2006, 2616; (c) Alcaide,
B.; Aly, M.; Rodríguez, C.; Rodríguez-Vicente, A. J. Org. Chem. 2000, 65, 3453.
13. Dejaegher, Y.; Mangelinkx, P.; De Kimpe, N. J. Org. Chem. 2002, 67, 2075.
14. General procedure for the retro-Staudinger reaction of 3a–c and 4a–c. Preparation
of 1a–c and 6a–c. Azeto-1,3-thiazine 3a–c or 4a–c (0.66 mmol) was dissolved
in dry MeOH (40 mL). To this stirred solution, NaOMe (71 mg, 1.32 mmol) was
added. The reaction mixture was stirred at reflux for 15 min. After evaporation,
the residue was dissolved in CH2Cl2 (20 mL). The organic phase was extracted
with H2O (10 mL), dried (Na2SO4) and evaporated. Compounds 1a–c are
known.18 The atom numbering of compounds 3 and 4 was also used for
products 6. Compound 6a: white crystalline powder, mp 197–198 °C (from
15. General procedure for the oxidation of 3a–c. Preparation of 4a–c. Compounds
3a–c (1.0 g) were suspended in AcOH (10 mL), followed by the addition of
freshly prepared peroxyacetic acid18 (15 mL). After complete dissolution, the
reaction mixture was allowed to stand at room temperature for 1 d and then
poured onto ice (30 g). The crystals that separated were removed by filtration,
and washed with cold H2O (5 mL) and MeOH (5 mL). Compound 4a: white
crystalline powder, mp 160–161 °C (from EtOH), yield 98%. mmax (KBr disc)
1808 (
benzene ring), 750
monosubstituted ring), 679 (CCl2) cmÀ1
m
C@O), 1316 (
m
asSO2), 1268 (
CArH, monosubstituted ring), 691
1H NMR d (500 MHz, CDCl3): 7.52
m
C–O), 1138 (
m
sSO2), 841 (
c
CArH, condensed
(c
(
c
CArCAr,
.
(2H, m, H-2’,6’), 7.47 (2H, m, H-3’,5’)*, 7.47 (1H, m, H-4’)*, 7.41 (1H, s, H-6), 7.07
(1H, s, H-9), 5.30 (1H, d, J = 13.8 Hz, SCH2), 4.55 (1H, d, J = 13.8 Hz, SCH2), 4.04
(3H, s, 8-OCH3), 3.99 (3H, s, 7-OCH3) ppm, * two overlapping signals; 13C NMR d
(125 MHz, CDCl3): 159.6 (C@O), 151.8 (C-8), 151.0 (C-7), 134.1 (C-1’), 131.4 (C-
5a), 130.5 (C-4’), 129.3 (C-3’), 128.8 (C-2’), 126.8 (C-9a), 112.9 (C-9), 106.3 (C-
6), 91.5 (C-1), 74.6 (C-9b), 59.2 (CH2) ppm. Anal. Calcd for C18H15Cl2NO5S
(428.29): C, 50.48; H, 3.53; N, 3.27; S, 7.49. Found: C, 50.36; H, 3.77; N, 3.42; S,
7.62. Compound 4b: white crystalline powder, mp 118–120 °C (from EtOH),
yield 94%. mmax (KBr disc) 1803 (
sSO2), 838 ( CArH, condensed benzene ring), 818 (
ring), 669 (CCl2) cmÀ1 1H NMR d (500 MHz, CDCl3): 7.44 (2H, m, H-2’,6’)*, 7.44
m
C@O), 1320 (
m
asSO2), 1262 (
mC–O), 1140
EtOH), yield 94%.
m
max (KBr disc) 1300 (
CArH, condensed benzene ring), 778 (
CArCAr, monosubstituted ring) cmÀ1 1H NMR d (500 MHz, CDCl3): 7.64 (2H,
m
asSO2), 1264 (
m
C–O), 1126 (
m
sSO2), 851
(m
c
c
CArH, para-disubstituted
(c
c
CArH, monosubstituted ring), 688
.
(c
.
(2H, m, H-3’,5’)*, 7.40 (1H, s, H-6), 6.98 (1H, s, H-9), 5.27 (1H, d, J = 13.8 Hz,
SCH2), 4.49 (1H, d, J = 13.8 Hz, SCH2), 4.04 (3H, s, 8-OCH3), 3.98 (3H, s, 7-OCH3)
ppm, * two overlapping signals; 13C NMR d (125 MHz, CDCl3): 159.4 (C@O),
151.9 (C-8), 151.1 (C-7), 136.9 (C-4’), 132.6 (C-1’), 131.3 (C-5a), 130.2 (C-2’),
129.5 (C-3’), 126.2 (C-9a), 112.6 (C-9), 106.4 (C-6), 91.4 (C-1), 74.1 (C-9b), 59.0
(CH2) ppm. Anal. Calcd for C18H14Cl3NO5S (462.73): C, 46.72; H, 3.05; N, 3.03; S,
6.93. Found: C, 46.97; H, 3.28; N, 3.19; S, 7.16; Compound 4c: white crystalline
m, H-2’,6’), 7.55 (1H, s, H-6), 7.54 (1H, m, H-4’), 7.49 (2H, m, H-3’,5’), 6.86 (1H,
s, H-9), 5.10 (2H, s, SCH2), 4.05 (3H, s, 7-OCH3), 3.78 (3H, s, 8-OCH3) ppm; 13C
NMR d (125 MHz, CDCl3): 166.9 (C-9b), 152.5 (C-8),* 152.4 (C-7),* 138.3 (C-1’),
131.4 (C-5a), 131.1 (C-4’), 129.4 (C-2’), 128.9 (C-3’), 123.8 (C-9a), 113.5 (C-10),
105.2 (C-6), 66.6 (CH2) ppm, * reversed assignments are also possible. Anal.
Calcd for C16H15NO4S (317.36): C, 60.55; H, 4.76; N, 4.41; S, 10.10. Found: C,
60.39; H, 5.01; N, 4.23; S, 10.31. Compound 6b: white crystalline powder, mp
powder, mp 220–221 °C (from EtOH), yield 97%. mmax (KBr disc) 1802 (
1317 ( asSO2), 1264 ( C–O), 1137 ( sSO2), 841 ( CArH, condensed benzene
ring), 814
CArH, para-disubstituted ring), 670 (CCl2) cmÀ1 1H NMR
mC@O),
232–233 °C (from EtOH), yield 93%.
1124 sSO2), 877 CArH, condensed benzene ring), 849
disubstituted ring) cmÀ1 1H NMR d (500 MHz, CDCl3): 7.59 (2H, m, H-2’,6’),
m
max (KBr disc) 1304 (
m
asSO2), 1277 (
m
C–O),
m
m
m
c
(
m
(c
(c
CArH, para-
(c
.
d
.
(500 MHz, CDCl3): 7.39 (1H, s, H-6), 7.37 (2H, m, H-2’,6’), 7.25 (2H, m, H-
3’,5’), 7.03 (1H, s, H-9), 5.26 (1H, d, J = 13.8 Hz, SCH2), 4.50 (1H, d, J = 13.8 Hz,
SCH2), 4.04 (3H, s, 8-OCH3), 3.98 (3H, s, 7-OCH3), 2.39 (3H, s, CH3) ppm; 13C
NMR d (125 MHz, CDCl3): 159.6 (C@O), 151.7 (C-8), 150.9 (C-7), 140.8 (C-4’),
131.4 (C-5a), 130.9 (C-1’), 130.0 (C-3’), 128.8 (C-2’), 127.0 (C-9a), 112.9 (C-9),
106.3 (C-6), 91.6 (C-1), 74.5 (C-9b), 59.1 (CH2), 21.5 (CH3) ppm. Anal. Calcd for
C19H17Cl2NO5S (442.31): C, 51.59; H, 3.87; N, 3.17; S, 7.25. Found: C, 51.45; H,
4.10; N, 3.41; S, 7.08.
7.53 (1H, s, H-6), 7.46 (2H, m, H-3’,5’), 6.81 (1H, s, H-9), 5.07 (2H, s, SCH2), 4.03
(3H, s, 7-OCH3), 3.79 (3H, s, 8-OCH3) ppm; 13C NMR d (125 MHz, CDCl3): 165.8
(C-9b), 152.6 (C-7), 152.5 (C-8), 137.4 (C-4’), 136.6 (C-1’), 131.5 (C-5a), 130.8
(C-2’), 129.2 (C-3’), 123.4 (C-9a), 113.1 (C-9), 105.3 (C-6), 66.6 (CH2) ppm. Anal.
Calcd for C16H14ClNO4S (351.81): C, 54.62; H, 4.01; N, 3.98; S, 9.11. Found: C,
54.81; H, 3.78; N, 4.13; S, 9.37. Compound 6c: white crystalline powder, mp
214–215 °C (from EtOH), yield 92%.
1124 sSO2), 875 CArH, condensed benzene ring), 829
disubstituted ring) cmÀ1 1H NMR d (500 MHz, CDCl3): 7.52 (1H, s, H-6),*
m
max (KBr disc) 1302 (
m
asSO2), 1277 (
mC–O),
(
m
(c
(c
CArH, para-
16. Holly, S.; Sohár, P. In Theoretical and Technical Introduction to the Series
Absorption Spectra in the Infrared Region; Láng, L., Prichard, W. H., Eds.;
Akadémiai Kiadó: Budapest, 1975; p 113 (a) p 113; (b) pp 128–129.
17. Wuts, P. G. M.; Greene, T. W. Protective Groups in Organic Synthesis; Wiley
Interscience: Hoboken, New Jersey, 2007.
.
7.51 (2H, m, H-2’,6’),* 7.27 (2H, m, H-3’,5’), 6.89 (1H, s, H-9), 5.06 (2H, s, SCH2),
4.02 (3H, s, 7-OCH3), 3.77 (3H, s, 8-OCH3), 2.43 (3H, s, CH3) ppm, * reversed
assignments are also possible; 13C NMR d (125 MHz, CDCl3): 166.8 (C-9b),
152.36 (C-8),** 152.32 (C-7),** 141.4 (C-4’), 135.4 (C-1’), 131.4 (C-5a), 129.6 (C-
3’), 129.4 (C-2’), 123.9 (C-9a), 113.6 (C-9), 105.2 (C-6), 66.6 (CH2), 21.8 (CH3)
18. Szabó, J.; Fodor, L.; Szücs, E.; Bernáth, G.; Sohár, P. Pharmazie 1984, 39, 426.