Reactions of 1,3-benzothiazines and 1,4-benzothiazepines with dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1007/s00706-010-0269-5

Substituted 2H-1,3-benzothiazines and 2,3-dihydro-1,4-benzothiazepines react with dimethyl acetylenedicarboxylate in aqueous methanol to give new, unexpected condensed-skeleton heterocycles. The structures of the new compounds were determined by ¹

Full text of DOI:10.1007/s00706-010-0269-5

Monatsh Chem (2010) 141:431–436
DOI 10.1007/s00706-010-0269-5
ORIGINAL PAPER
Reactions of 1,3-benzothiazines and 1,4-benzothiazepines
with dimethyl acetylenedicarboxylate
•
Lajos Fodor Peter Csomos Gabor Bernath
•
•
´
Pal Sohar Tamas Holczbauer Alajos Kalman
´
´
´
•
•
´
´
´
´
´
Received: 30 October 2009 / Accepted: 13 February 2010 / Published online: 18 March 2010
Ó Springer-Verlag 2010
Abstract Substituted 2H-1,3-benzothiazines and 2,3-
dihydro-1,4-benzothiazepines react with dimethyl acety-
lenedicarboxylate in aqueous methanol to give new,
unexpected condensed-skeleton heterocycles. The struc-
Keywords Sulfur and nitrogen heterocycles ꢀ
Dimethyl acetylenedicarboxylate ꢀ NMR spectroscopy ꢀ
X-ray structure determination
1
tures of the new compounds were determined by H and
13C nuclear magnetic resonance (NMR), two-dimensional
(2D) heteronuclear multiple-bond correlation (HMBC),
infrared (IR), and for one derivative also by X-ray
analysis.
Introduction
Following the pioneering discovery by Diels and Alder
[1], the reactions of dimethyl acetylenedicarboxylate
(DMAD) with heterocyclic compounds have been the
subject of a great number of publications [2, 3]. A
majority of the reactions have been carried out on
heteroaromatic systems such as pyridines, quinolines,
isoquinolines, thiazoles, imidazoles, phenanthridines,
quinoxalines, pyridazines, and their substituted derivatives
[2–11]. DMAD is known to react with imines to give a
variety of products, depending on the nature of the imine
and the reaction conditions. The reaction is highly solvent
dependent, and the addition depends on the polarity of the
solvent applied.
´ ´
Professor Gabor Bernath died on 1 October 2009.
´
L. Fodor (&) ꢀ P. Csomos
Central Laboratory, County Hospital, Gyula, Hungary
e-mail: fodor@pandy.hu
´
L. Fodor ꢀ P. Csomos
Institute of Pharmaceutical Chemistry, University of Szeged,
Szeged, Hungary
We earlier reported that cycloaddition of 6,7-dimethoxy-
2H-1,3-benzothiazine with DMAD in an aprotic solvent
such as diethyl ether led to a 1:2 adduct, 2,3-dimethoxy-
pyrido[1,2-c][1,3]benzothiazine-8,9,10,11-tetracarboxylic
acid tetramethyl ester [12]. However, the reaction of 6,7-
dimethoxy-2H-1,3-benzothiazine with DMAD in refluxing
aqueous methanol yielded not the expected product,
but ( )-2,3,10,11-tetramethoxy-6H,8H,13aH-[1,3]benzo-
thiazino[4,3-b][1,3]benzothiazine (5,13-dithiaxylopinine)
and 6,7-dimethoxy-3-methoxycarbonyl-2H-benzo[b]thio-
pyran [13]. As a continuation of our investigations on the
reactions of sulfur- and nitrogen-containing condensed-
skeleton heterocycles including different cycloadditions
[12–15], in the present paper we report on the reactions
of 1,3-benzothiazines (1a–1c, 1e, 1f) [16, 17] and
´
L. Fodor ꢀ P. Csomos
Research Group of Stereochemistry, Hungarian Academy
of Sciences, Szeged, Hungary
´
P. Sohar (&)
Department of Chemistry, Eotvos Lorand University,
´
¨
¨
Budapest, Hungary
e-mail: sohar@chem.elte.hu
´
P. Sohar
Protein Modelling Research Group, Hungarian Academy
´
of Sciences, Eotvos Lorand University, Budapest, Hungary
¨
¨
´
´
T. Holczbauer ꢀ A. Kalman
Institute of Structural Chemistry, Chemical Research Centre,
Hungarian Academy of Sciences, Budapest, Hungary
123

432
L. Fodor et al.
1,4-benzothiazepines (1d, 1g) [18] with DMAD in aqueous
methanol.
The structures of the reaction products were proved by
NMR spectroscopy and by X-ray crystallography as dis-
cussed below. In these reactions, the heterocyclic
compounds 1a–1d reacted as imines, most probably via
intermediates 3a–3d [25]; thus pyrrolo-1,3-benzothiazines
7a–7c (Z form) and 1,4-benzothiazepine 7d (Z form) were
formed in good yields (Scheme 1).
Results and discussion
Chemistry
Similarly as for 1a–1d, in the reactions of aryl-substi-
tuted 1,3-benzothiazines (1e, 1f) or 1,3-benzothiazepine
(1g) with DMAD, several structures come into consider-
ation as possible products (e.g., 9, 10, 13, 14) (Scheme 2).
In these cases, 4-aryl-2H-1,3-benzothiazines (1e, 1f) or 2,3-
dihydro-7,8-dimethoxy-5-phenyl-1,4-benzothiazepine (1g)
reacted with DMAD in aqueous methanol to furnish only
one product. Oxazolo-1,3-thiazines 14e, 14f (Z form) and
oxazolo-1,4-thiazepine 14g (Z form) were obtained in good
yields (Scheme 2).
In recent years, there has been considerable interest in
investigations of the reactivity of nitrogen-containing
heterocycles with DMAD, and with DMAD in a multi-
component reaction [19–24]. As
appeared worthwhile to study the reactions of 4-alkyl- and
4-aralkyl-6,7-dimethoxy-2H-1,3-benzothiazine (1a–1c)
a consequence, it
and 5-methyl-7,8-dimethoxy-2,3-dihydro-1,4-benzothiaze-
pine (1d), because these molecules are capable of reacting
as cyclic imines or as secondary enamines (Scheme 1).
When 1a–1d were reacted with DMAD in methanol, only
one product was formed.
As concerns the possible reaction mechanism, the above
results clearly indicate that in these reactions the initial
addition product is the corresponding zwitterion [26] 12
formed from the benzothiazine or benzothiazepine and
DMAD, which can be trapped very effectively with water
to form 11, and lead by ring closure to 14e–14g. Alterna-
tively, for similar structures, another possible route has
been proposed via the related intermediate 12 [9].
To summarize, the cycloadditions of substituted 2H-1,
3-benzothiazines (1a–1c, 1e, 1f) and 2,3-dihydro-1,4-ben-
zothiazepines (1d, 1g) with dimethyl acetylenedicarboxylate
in aqueous methanol provided new, unexpected condensed-
skeleton pyrrolo- and oxazolothiazine and thiazepine
(7a–7d and 14e–14g) heterocycles.
Elemental analysis clearly revealed that the products
were formed by the addition of one molecule of DMAD to
one molecule of benzothiazine or benzothiazepine, with
elimination of one molecule of methanol. Several struc-
tures can be presumed for such a product. In the reactions
of benzothiazines 1a–1c and benzothiazepine 1d, there are
possibilities for the formation of various isomers of 4–7
which would behave very similar spectroscopically
(Scheme 1). Likely isomeric products would be 4, 5 if the
reaction took place through the enamine tautomer of
1a–1d, and 6, 7 if it involved participation of the imine
form (Scheme 1).
Scheme 1
MeO
MeO
S
MeO
MeO
S
MeO
MeO
S
(CH2)n
N
(
)
n
(
)
CH2 n
NH
CH2
N
O
R
R
R
1a-1d
CHCOOMe
4a-4d ( /
DMAD H2O, MeOH
H2O, MeOH
DMAD
)
Z E
MeO
MeO
(CH2)n
NH
MeO
S
(
)
MeO
MeO
S
CH2 n
N
COOMe
(
)
n
CH2
N
COOMe
O
MeO
COOMe
R
COOMe
R
R
3a-3d
2a-2d
COOMe
5a-5d
MeO
MeO
S
MeO
MeO
S
MeO
MeO
S
(
)
(
)
CH2 n
(
)
CH2
N
CH2
n H
n COOMe
N
COOMe
N
COOMe
H
R
R
R
O
O
O
6a 6d
-
7a-7d (
)
E
7a-7d (
)
Z
a
b
c
d
: n = 1, R = H; : n = 1, R = Me; : n =1; R = Ph; : n = 2, R = H
123

Reactions of 1,3-benzothiazines and 1,4-benzothiazepines
433
Scheme 2
MeO
MeO
S
MeO
MeO
S
MeO
MeO
S
(
)
CH2
n H
COOMe
(
)
n
CH2
(
)
CH2
n
N
N
O
N
COOMe
Ar
Ar
Ar
O
O
O
O
COOMe
O
9e 9g
-
14e 14g
13e 13g
-
(
E
)
-
MeO
S
MeO
MeO
S
MeO
MeO
S
(CH2)n
(CH2)n
N
COOMe
DMAD
(CH2)n
N
DMAD
N
O
H2O
MeOH
H2O
MeOH
MeO
Ar
Ar
OH
OH COOMe
Ar
COOMe
11e 11g
-
1e 1g
-
8e 8g
-
1
8
2
MeO
MeO
S
MeO
MeO
S
8a
4a
COOMe
MeO
S
(
)
n
CH2
(CH2)n
N
(
)
CH2
3
n COOMe
7
6
N
4
N
O
MeO
5 Ar
H
Ar
O
Ar
H
O
O
O
H
OMe
CHCOOMe
O
10e-10g
/
12e-12g
14e-14g ( )
Z
(Z E)
e
f
g
: n = 1, Ar = 2-Cl-C6H4; : n = 1, Ar = 4-NO2-C6H4; : n= 2, Ar = Ph
Structure
The spectral data (IR, H, and 13C NMR) unambiguously
confirm the structures. Only the following remarks are
necessary. As far as structures 4–7 are concerned, because
of the mesomerism the carbonyl carbon in the enamino-
carbonyl (types 4 and 7) and pyridone (types 5 and 6)
derivatives displays irregular IR frequencies and 13C NMR
chemical shifts. Hence, it is not possible to differentiate
between the potential structural isomers merely on the
basis of routine spectral data. Accordingly, to reach a
decision on the structures, C,H-correlations via long-range
couplings (HMBC) [26, 27] were used.
1
Fig. 1 Ortep plot of 7b with atomic labeling
The 13C NMR line at 166.7 ppm for product c must be
assigned to the ester carbonyl, as proven by the C,H-shift
correlation in the HMBC spectrum with the signal of the
methoxy hydrogens at 3.78 ppm. The other carbonyl line at
187.6 ppm correlates with the 1H NMR signal of the
C-methyl hydrogens (2.07 ppm) and the heterocyclic (6)
=CH– or exocyclic (7) hydrogen (6.03 ppm). This suggests
structure 6 or 7. To choose between them, however, is not
possible simply from routine IR and NMR spectral data.
The 187.6 ppm 13C NMR shift lies on the borderline
characteristic of amides (165–186 ppm) and ketones (186–
210 ppm) [28]. Therefore, the crystal structure was deter-
mined by X-ray crystallography for one (b) of these
compounds (a–d). The results proved structure 7b (Fig. 1).
The very similar spectral data of the analogous products a
and c and the thiazepine homolog confirmed identical
constitutions, i.e., structures 7a–7d.
esters and d-lactones cannot have such an IR band [30].
Consequently, only the c-lactam or c-lactone structures (10
and 14) are in accordance with the spectral data. Similarly
as for 4–7, we applied the HMBC method (for product f) to
decide between structures 10 and 14. The line of the sp2
carbon in ring C is at 150.5 ppm. This signal also gives
cross-peaks with both methylene hydrogens, the latter
further yielding cross-peaks with the C-4 and C-8a lines at
94.9 and 124.6 ppm, respectively. Consequently, the for-
mer carbon must be bonded to N-3. Structure 14f follows
unambiguously. Structure 10 can be excluded on the basis
of the chemical shift of the carbon in question. The -I effect
of the attached oxygen in 10 should cause a significantly
higher downfield shift of the line of this C atom. The
analogous structures of 14e–14g, similarly as in the case of
7a–7d, are obvious from their very similar spectral
parameters.
The molecules formed from 1e–1g have very high IR
carbonyl frequencies (1,798–1,804 cm–1). Conjugated
123

434
L. Fodor et al.
All of the new compounds synthesized (7a–7d, 14e–
14g) contain carbomethoxymethylidene side-chain
and tetramethylsilane (TMS) as internal reference. Distor-
tionless enhancement by polarization transfer (DEPT)
spectra were run in a standard manner, using only the
h = 135° pulse to separate the CH/CH3 and CH2 lines
phased ‘‘up’’ and ‘‘down,’’ respectively. The 2D HMBC
spectra were obtained on a Bruker DRX 500 spectrometer
by using the standard Bruker pulse programs. Results of
elemental analyses agreed favorably with calculated val-
ues. 1,3-Benzothiazines (1a–1c, 1e, 1f) [16, 17] and 1,4-
benzothiazepines (1d, 1g) [18] were prepared by literature
methods.
a
(=CHCOOMe). Thus, the geometric isomerism must be
clarified. The chemical evidence suggests the preference of
the Z form because of the unfavorable interaction between
the ring carbonyl (ketone or lactone) and the ester oxygens
in the side-chain. In accordance, the X-ray measurements
on 7b supplied proof of this steric structure, and the anal-
ogous structure follows from the very similar NMR spectra
of 7a, 7c, and 7d. For 14f, we carried out DIFFNOE
measurements, which provided indirect proof of the Z form
for this compound too.
The quasi-equatorial methylene-H in 14f is coplanar and
close to the ester carbonyl, the anisotropy causing the
irregular downfield shift of its signal (to 6.32 ppm). The
unambiguous assignment of this signal was confirmed by
the DIFFNOE measurements, demonstrating the close-
lying position of the axial counterpart to the aryl group.
Due to the diaxial and near orientation of the methylene-H
in question and the aryl ring, irradiation (at 4.75 ppm)
resulted in an intensity enhancement for the ortho-hydro-
gens in the Ar substituent.
General procedure for preparation
of pyrrolinobenzothiazine derivatives 7a–7d
Compound 1a–1d (2.5 mmol) was dissolved in aqueous
methanol (25 cm3 methanol and 2 cm3 water), and a
solution of DMAD (2.5 mmol) in 10 cm3 methanol was
added dropwise with stirring during 1 h. The mixture was
allowed to stand at room temperature for 3 h. The metha-
nol solution was evaporated, and the residue was
crystallized from methanol/acetone to yield colorless
crystals.
The drastic differences in the C-4 chemical shifts for
structures 7a–7d (158–176 ppm) and 14e–14g (87–
96 ppm) are in accordance with the change in the hybrid
state of this carbon from sp2 to sp3 (the numbering of
rings A and B in 1a–1c, 1e, 1f is also used for 1d, 1g in the
text and the experimental part, cf. Scheme 2).
Methyl (Z)-(8,9-dimethoxy-2-oxo-5H-pyrrolo[1,2-c][1,3]-
benzothiazin-3(2H)-ylidene)acetate (7a, C16H15NO5S)
1
M.p.: 206–207 °C (from methanol); yield 76%; H NMR
(250 MHz, CDCl3): d = 7.09 (s, H-5), 6.83 (s, H-8), 6.07
(s, =CH– heteroring), 5.72 (s, =CH–), 5.52 (s, CH2), 3.95
(s, OMe pos. 7), 3.92 (s, OMe pos. 6), 3.79 (s, OMe ester
group) ppm; 13C NMR (80 MHz, CDCl3): d = 185.4 (C=O
ketone), 166.4 (C=O ester), 164.3 (C-4), 152.9 (C-7), 148.1
(C-6), 142.4 (quaternary C in heteroring), 129.2 (C-8a),
116.6 (C-4a), 111.3 (C-8*), 110.5 (C-5*), 99.0 (=CH–
exocyclic group), 96.7 (=CH– exocyclic group), 56.2 (OMe
pos. 7), 56.1 (OMe pos. 6), 52.0 (OMe ester), 44.5 (C-2)
ppm (*interchangeable assignments); IR (KBr): vꢀ = 1,684
Due to the molecular symmetry (Cs) of 7a–7c, the 2-
methylene hydrogens are chemically equivalent (they give
1
a H NMR singlet), while the nonplanar structure of the
thiazepine ring in 7d and 14g is revealed in the non-
equivalence of these hydrogens, with an AB-type spectrum.
The hydrogens of both methylene groups in 14e, 14f are
also nonequivalent because of the presence of a chiral
center (C-4) in these molecules.
It is noteworthy that the anisotropy of the phenyl sub-
stituent [29] in 7c causes upfield shifts of the H-5 and 6-
methoxy signals. This effect is more pronounced in 14e,
14f than in 14g, in which H-5 and the phenyl ring are more
distant from one another in the preferred conformation.
(C=O ester and C=O ketone; overlapping signals) cm-1
.
Methyl (Z)-(8,9-dimethoxy-1-methyl-2-oxo-5H-pyrrolo-
[1,2-c][1,3]benzothiazin-3(2H)-ylidene)acetate
(7b, C17H17NO5S)
1
M.p.: 210–211 °C (from methanol); yield 68%; H NMR
(250 MHz, CDCl3): d = 7.25 (s, H-5), 6.91 (s, H-8), 6.03
(s, =CH–), 5.49 (s, CH2), 3.95 (s, OMe pos. 7), 3.93 (s,
OMe pos. 6), 3.78 (s, OMe ester group), 2.07 (s, Me) ppm;
13C NMR (80 MHz, CDCl3): d = 187.6 (C=O ketone),
166.7 (C=O ester), 158.2 (C-4), 151.3 (C-7), 147.6 (C-6),
140.3 (quaternary C in heteroring), 129.6 (C-8a), 118.8 (C-
4a), 112.9 (C-8*), 111.4 (C-5*), 106.2 (=C-R), 97.50
(=CH– exocyclic group), 56.2 (OMe pos. 7), 56.1 (OMe
pos. 6), 52.0 (OMe ester), 45.2 (C-2), 8.7 (CCH3) ppm
(*interchangeable assignments); IR (KBr): vꢀ = 1,700
Experimental
General
The IR spectra were recorded in KBr pellets with a Bruker
1
IFS 55 FT spectrometer. The H and 13C NMR spectra
were recorded in CDCl3 or dimethyl sulfoxide (DMSO)-d6
solution in 5 mm tubes at room temperature (RT) on a
Bruker WM-250 spectrometer at 250 (1H) and 63 (13C)
MHz, with the deuterium signal of the solvent as the lock
(C=O ester), 1,669 (C=O ketone) cm-1
.
123

Reactions of 1,3-benzothiazines and 1,4-benzothiazepines
435
Methyl (Z)-(8,9-dimethoxy-1-phenyl-2-oxo-5H-pyrrolo-
[1,2-c][1,3]benzothiazin-3(2H)-ylidene)acetate
(7c, C22H19NO5S)
(s, H-5), 6.55 (d, J = 13.5 Hz, CH2, 1H), 5.81 (s, =CH–),
4.65 (d, J = 13.5 Hz, CH2, 1H), 3.89 (s, OMe pos. 7), 3.79
(s, OMe pos. 6), 3.73 (s, OMe ester group) ppm; 13C NMR
(80 MHz, CDCl3): d = 166.6 (C=O ester), 164.7 (C=O
lactone), 150.4 (quaternary C in heteroring), 150.3 (C-7),
147.0 (C-6), 134.0 (C-60, 2-chlorophenyl), 133.7 (C-20, 2-
chlorophenyl), 133.6 (C-10, 2-chlorophenyl), 132.8 (C-50,
2-chlorophenyl), 132.6 (C-40, 2-chlorophenyl), 131.5 (C-30,
2-chlorophenyl), 124.3 (C-8a), 122.5 (C-4a), 112.5 (C-8*),
108.8 (C-5*), 96.0 (C-4), 91.1 (=CH-), 56.0 (OMe, pos. 7),
55.9 (OMe, pos. 6), 51.5 (OMe ester), 43.6 (C-2) ppm
(*interchangeable assignments); IR (KBr): vꢀ = 1,798
1
M.p.: 226–228 °C (from methanol); yield 71%; H NMR
(250 MHz, CDCl3): d = 7.40–7.20 (5H, m, Ph), 6.85 (s, H-
5*), 6.82 (s, H-8*), 6.14 (s, =CH–), 5.56 (s, CH2), 3.91 (s,
OMe pos. 7), 3.80 (s, OMe pos. 6), 3.23 (s, OMe ester
group) ppm (*interchangeable assignments); 13C NMR
(80 MHz, CDCl3): d = 185.2 (C=O ketone), 166.5 (C=O
ester), 158.1 (C-4), 151.7 (C-7), 146.9 (C-6), 140.3
(quaternary C in heteroring), 131.3 (C40, phenyl), 130.1
(C-20,60, phenyl), 129.7 (C-8a), 128.6 (C-30,50, phenyl),
127.3 (C-10, phenyl), 117.2 (C-4a), 113.8 (C-8*), 111.8
(=C-R), 111.0 (C-5*), 98.5 (=CH– exocyclic group), 56.0
(OMe pos. 7), 54.9 (OMe pos. 6), 52.0 (OMe ester), 45.0
(C-2) ppm (*interchangeable assignments); IR (KBr):
(C=O lactone), 1,694 (C=O ester), 1,645 (C=C) cm-1
.
Methyl (Z)-[8,9-dimethoxy-10b-(4-nitrophenyl)-2-oxo-
5H,10bH-oxazolo[3,2-c][1,3]benzothiazin-3(2H)-ylidene]-
acetate (14f, C21H18N2O8S)
vꢀ = 1,701 (C=O ester), 1,675 (C=O ketone) cm-1
.
1
M.p.: 176–177 °C (from methanol); yield 69%; H NMR
(250 MHz, CDCl3): d = 8.26 (d, J = 9 Hz, H-20,60,
4-nitrophenyl), 7.54 (d, H-30,50, 4-nitrophenyl), 6.72 (s,
H-8), 6.65 (s, H-5), 6.32 (d, J = 13.5 Hz, CH2, 1H), 5.86
(s, =CH–), 4.75 (d, J = 13.5 Hz, CH2, 1H), 3.90 (s, OMe
pos. 7), 3.78 (s, OMe pos. 6), 3.74 (s, OMe ester group)
ppm; 13C NMR (80 MHz, CDCl3): d = 166.2 (C=O ester),
164.1 (C=O lactone), 150.5 (quaternary C in heteroring),
148.7 (C-7), 147.5 (C-6), 144.8 (C-40, 4-nitrophenyl), 134.3
(C-10, 4-nitrophenyl), 128.8 (C-20,60, 4-nitrophenyl), 124.6
(C-8a), 123.7 (C-30,50, 4-nitrophenyl), 121.7 (C-4a), 112.0
(C-8*), 109.4 (C-5*), 94.9 (C-4), 93.2 (=CH-), 56.0 (OMe
pos. 6 and 7, overlapping signals), 51.7 (OMe ester), 44.3
(C-2) ppm (*interchangeable assignments); IR (KBr):
vꢀ = 1,804 (C=O lactone), 1,692 (C=O ester), 1,649 (C=C)
Methyl (Z)-(5,6-dihydro-9,10-dimethoxy-2-oxopyrrolo-
[1,2-d][1,4]benzothiazepin-3(2H)-ylidene)acetate
(7d, C17H17NO5S)
M.p.: 190–191 °C (from methanol/acetone); yield 74%; 1H
NMR (250 MHz, CDCl3): d = 7.28 (s, H-5), 7.15 (s, H-8),
6.04 (s, =CH– heteroring), 5.48 (s, =CH–), 4.16 (triplet-
like signal, CH2), 3.95 (s, OMe pos. 7), 3.92 (s, OMe pos.
6), 3.78 (s, OMe ester group), 3.43 (triplet-like signal, CH2)
ppm; 13C NMR (80 MHz, CDCl3): d = 186.8 (C=O
ketone), 175.4 (C-4), 166.1 (C=O ester), 151.6 (C-7),
149.4 (C-6), 142.8 (quaternary C in heteroring), 127.2 (C-
8a), 123.9 (C-4a), 118.0 (C-5*), 112.6 (C-8*), 99.9 (=CH-),
98.6 (=CH-), 56.1 (OMe pos. 6 and 7, overlapping signals),
51.8 (OMe ester), 45.1 (NCH2), 36.6 (SCH2) ppm (*inter-
changeable assignments); IR (KBr): vꢀ = 1,712 (C=O
cm-1
.
ester), 1,682 (C=O ketone) cm-1
.
Methyl (Z)-(5,6-dihydro-9,10-dimethoxy-2-oxo-11b-phenyl-
10bH-oxazolo[3,2-d][1,4]benzothiazepin-3(2H)-ylidene)-
acetate (14g, C21H21NO6S)
General procedure for preparation
of oxazolidinobenzothiazine derivatives 14e–14g
1
M.p.: 143–144 °C (from methanol); yield 72%; H NMR
(250 MHz, CDCl3): d = 7.40 (m, H-30,40,50, phenyl), 7.20
(d, H-20,60, phenyl), 7.07 (s, H-8*), 7.05 (s, H-5*), 5.57 (s,
=CH–), 5.20 (m, NCH2, 1H), 3.91 (s, OMe pos. 7), 3.82 (s,
OMe pos. 6), 3.68 (s, OMe ester group), 3.65 (m, NCH2,
1H), 3.30 (s, SCH2, 1H), 2.85 (s, SCH2, 1H) ppm
(*overlapping signals); 13C NMR (80 MHz, CDCl3):
d = 166.6 (C=O ester), 164.4 (C=O lactone), 148.7
(quaternary C in heteroring and C-7, overlapping signals),
148.2 (C-6), 138.1 (C-10, phenyl), 135.7 (C-4a), 128.6 (C-
30,50, phenyl), 128.1 (C-20,60, phenyl), 124.7 (C-8a), 124.3
(C-8a), 117.0 (C-5**), 112.5 (C-8**), 100.8 (=CH–), 87.2
(C-4), 56.0 (OMe pos. 6 and 7, overlapping signals), 51.1
(OMe ester), 49.5 (NCH2), 33.0 (SCH2) ppm (**inter-
changeable assignments); IR (KBr): vꢀ = 1,799 (C=O
Compound 1e–1g (2.5 mmol) was dissolved in aqueous
methanol (25 cm3 methanol and 2 cm3 water), and DMAD
(2.5 mmol) was added. The solution was stirred under
reflux for 5 min and then left to stand for 3 h. The pre-
cipitated dark-red crystals were filtered off and washed
with methanol.
Methyl (Z)-[10b-(2-chlorophenyl)-8,9-dimethoxy-2-oxo-
5H,10bH-oxazolo[3,2-c][1,3]benzothiazin-3(2H)-ylidene]-
acetate (14e, C21H18ClNO6S)
1
M.p.: 159–160 °C (from methanol); yield 66%; H NMR
(250 MHz, CDCl3): d = 7.50 (dd, H-30, 2-chlorophenyl),
7.35 (t, H-40, 2-chlorophenyl), 7.20 (t, H-50, 2-chloro-
phenyl), 7.10 (d, H-60, 2-chlorophenyl), 6.83 (s, H-8), 6.59
lactone), 1,703 (C=O ester), 1,646 (C=C) cm-1
.
123

436
L. Fodor et al.
6. Lin Q, Djaidi D, Bishop R, Craig DC, Scudder ML (1998) Aust J
Chem 51:799
X-ray analysis of 7b (Fig. 1)
7. Yamamoto H, Kobayashi T, Nitta M (1998) Heterocycles
48:1903
8. Kawasaki T, Tang C-Y, Koizumi E, Nakanishi N, Sakamoto M
(1998) Heterocycles 48:975
The data were collected on a Rigaku Rapid Series diffrac-
tometer equipped with a Cu X-ray tube and a graphite crystal
monochromator. Triclinic space group P-1 (No. 2) with
9. Heaney F, Kelly BM, Bourke S, Rooney O, Cunningham D,
McArdle P (1999) J Chem Soc Perkin Trans 1:143
10. Nair V, Speekanth AR, Biju AT, Rath NP (2003) Tetrahedron
Lett 44:729
˚
˚
˚
a = 8.6461(3) A, b = 8.7105(2) A, c = 10.4572(3) A,
a = 100.777(2)°, b = 91.619(2)°, c = 93.212(2)°, V =
771.84(4) A , Z = 2, dcalc = 1.495 g cm-3, l = 2.125
3
˚
mm-1. A total of 13,384 reflections were collected, of which
2,700 were unique (Rint = 0.057), and corrected for
absorption. The structure was solved by using the SHELX97
and SHELXL97 programs. The resulting structural param-
eters were refined to convergence of R1 = 0.0404 for 2,531
independent reflections with I [ 2r(I), using full-matrix
least-squares techniques and a structural model which
incorporated anisotropic vibrational parameters for all non-
hydrogen atoms and isotropic thermal parameters for all
hydrogen atoms. CCDC 736565 contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.
ac.uk, or by contacting The Cambridge Crystallographic
Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:
?44 1223 336033.
11. Nair V, Deviprija S, Suresh E (2008) Tetrahedron 64:3567
´
´
´
12. Fodor L, Szabo J, Bernath G, Sohar P (1982) Heterocycles 19:488
13. Fodor L, Bernath G, Sohar P, Groschl D, Meier H (2006) Mon-
´
´
¨
atsh Chem 137:231
14. Fodor L, MacLean DB (1987) Can J Chem 65:18
´
´
15. Csomos P, Fodor L, Bernath G, Sinkkonen J, Salminen J,
¨
Wiinamaki K, Pihlaja K (2008) Tetrahedron 64:1002
´
´ ´
16. Szabo J, Fodor L, Szucs E, Bernath G, Sohar P (1984) Pharmazie
}
39:426
´
´
17. Szabo J, Fodor L, Varga I, Vinkler E, Sohar P (1977) Acta Chim
Acad Sci Hung 93:403
´
´ ´
18. Szabo J, Bernath G, Katocs A, Fodor L, Sohar P (1987) Can J
´
Chem 65:175
19. Nair V, Menon RS, Sreekumar V (2005) Pure Appl Chem
77:1191
20. Nair V, Menon RS, Shrekanth AR, Abhilash N, Biju AT (2006)
Acc Chem Res 39:520
21. Vedensky VY, Ivanov YV, Kysil V, Williams C, Tkachenko S,
Kiselyov A, Khvat AV, Ivachtchenko AV (2005) Tetrahedron
Lett 46:3953
22. Yadav JS, Reddy BVS, Yadav NN, Gupta MK (2008) Tetrahe-
dron Lett 49:2815
23. Terzidis MA, Stephanidou-Stephanatou J, Tsoleridis CA (2009)
Tetrahedron Lett 50:1196
Acknowledgments The authors express their thanks to the Hun-
garian Scientific Research Foundation (OTKA) for financial support
(OTKA grants T049712 and K-68887). We are indebted to Dr. A.
24. Yavari I, Piltan M, Moradi L (2009) Tetrahedron Lett 50:2067
25. Huisigen R (1969) In: Castle R (ed) Topics in heterocyclic
chemistry, chapter 8. Wiley, New York, p 223
26. Bax A, Morris G (1981) J Magn Res 42:501
27. Kessler H, Griesinger C, Zarboch J, Loosi H (1984) J Magn Res
57:331
´
´
Csampai for measuring the NMR and IR spectra and to Ms. E. Juhasz
Dinya for technical assistance. The authors also thank Mr. Gy. Argay
for assistance.
References
´
28. Sohar P (1983) Nuclear magnetic resonance spectroscopy, vol 2.
CRC Press, Boca Raton, p 180
1. Diels O, Alder K, Nienborg N, Schmalbeck O (1931) Ann Chem
490:243
´
29. Sohar P (1983) Nuclear magnetic resonance spectroscopy, vol 1.
CRC Press, Boca Raton, pp 35–38
2. Acheson RM, Elmore NF (1978) Adv Heterocycl Chem 23:263
3. Acheson RM (1982) J Heterocycl Chem 19(supplement):59
4. Djaidi D, Bishop R, Craig DC, Scudder ML (1999) J Chem Soc
Perkin Trans 1:1859
´
30. Holly S, Sohar P (1995) In: Lang L, Prichard WH (eds) Theo-
retical and technical introduction to the series absorption spectra
´
´ ´
in the infrared region. Akademiai Kiado, Budapest, pp 100–102
5. Lin Q, Ball GE, Bishop R (1997) Tetrahedron 53:10899
123