From benzil arylimines to 2H-benzo-1,4-thiazines, benzothiazoles or indoles

Article abstract of DOI:10.1016/S0040-4020(01)00317-9

A series of benzil monoarylimines (1) was treated with phosphorus pentasulfide in refluxing toluene or xylene. Thionation of 1 occurred readily to afford either 2H-benzo-1,4-thiazines (2) or indoles (4) via annulation reactions, depending strongly on the nature of the meta substituent of the arylamino group. Mechanisms for these rearrangements were proposed. Furthermore, subsequent oxidation of 2 provided benzothiazoles (3). All compounds were fully characterized by IR, MS, ¹³C and ¹H NMR.

Full text of DOI:10.1016/S0040-4020(01)00317-9

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 4195±4202
From benzil arylimines to 2H-benzo-1,4-thiazines,
benzothiazoles or indoles
Jean-Damien Charrier, Cyrille Landreau, David Deniaud, FrancËoise Reliquet,
Alain Reliquet and Jean Claude Meslinp
Á Â Á
Laboratoire de Synthese Organique, UMR CNRS 6513, Faculte des Sciences et des Techniques, 2, rue de la Houssiniere, BP 92208,
44072 Nantes Cedex, France
Received 20 November 2000; revised 1 February 2001; accepted 13 March 2001
AbstractÐA series of benzil monoarylimines (1) was treated with phosphorus pentasul®de in re¯uxing toluene or xylene. Thionation of 1
occurred readily to afford either 2H-benzo-1,4-thiazines (2) or indoles (4) via annulation reactions, depending strongly on the nature of the
meta substituent of the arylamino group. Mechanisms for these rearrangements were proposed. Furthermore, subsequent oxidation of 2
provided benzothiazoles (3). All compounds were fully characterized by IR, MS, 13C and 1H NMR. q 2001 Elsevier Science Ltd. All rights
reserved.
1. Introduction
In the course of our ongoing studies on heterodienic
synthons,6 we have previously described that thionation
of benzil monohydrazones led to 3,6-dihydro-2H-1,3,4-
thiadiazines by rearrangement.7 Obviously, the nucleo-
philic properties of sulfur were assumed to induce cycli-
zation of the corresponding thiocarbonyl derivatives
(Scheme 1).
A number of polysubstituted polyheterocyclic compounds
display signi®cant pharmacological activities. Among
those, benzo-1,4-thiazines,1 benzothiazoles2 or indoles3
have been extensively investigated. For example, highly
substituted indoles were recently tested for antiin¯amma-
tory, ulcerogenic and antispasmodic activities4 whereas a
methotrexate derivative bearing a benzothiazine moiety
was successfully evaluated as an antirheumatic agent1b.
Furthermore, 2-arylbenzothiazoles are currently con®rmed
as a novel class of potent and selective antitumor agents5.
Therefore, it looks important to search for new methods to
synthesize such compounds.
These considerations in mind, we decided to extend this
activation method to further 1-oxa-4-azadienes. On the
other hand, we planned to develop a novel approach to
build complex condensed heterocyclic compounds. a-Aryl-
iminoketones were consequently thought to be suitable
candidates for such investigations (Scheme 2).
Scheme 1.
Scheme 2.
Keywords: sulfuration; cyclization; benzothiazines; benzothiazoles; indoles.
Corresponding author. Tel.: 133-2-51-12-54-05; fax: 133-2-51-12-54-02; e-mail: meslin@chimie.univ-nantes.fr
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00317-9

4196
J.-D. Charrier et al. / Tetrahedron 57 62001) 4195±4202
Scheme 3.
Table 1. Benzil arylimines 1
Compd
Ar
R2
R3
R4
R5
Yield (%)
mp (8C)a (Lit.)Ref.
1a
1b
1c
1d
1e
1f
1g
1h
1i
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
H
H
H
H
H
H
H
OCH3
H
H
H
H
H
OCH3
H
H
H
H
OCH3
OCH3
H
Cl
H
CH3
H
OCH3
SCH3
N(CH3)2
OCH3
OCH3
OCH3
N(C2H5)2
N(CH3)2
N(C2H5)2
H
H
H
H
H
H
H
H
H
68
68
80
68
68
73
78
66
66
69
71
75
62
101±103 (98±100)9,10
117±119 (104±106)9,10
111±113 (110)9,10
86±87
115±118 (114±116)9,10
73±76
141±143 (134±136)10
105±106
87±89
1j
1k
1l
OCH3
H
H
yellow oil
120±121
140±141
170±171
H
H
H
p-CH3OC6H4
p-CH3OC6H4
H
H
1m
H
a
Compounds 1a±f, h, j: yellow crystals, 1g, k, m: red crystals, 1l: orange crystals.
The aim of this paper is to report a part of our work directed
to the preparation of benzil arylimines (1) substituted with
dialkylamino, methoxy or methylsulfanyl groups in differ-
ent positions on the ring and to the transformation of these
compounds into interesting heterocycles via sulfuration
reaction of their carbonyl group.
accomplished according to a procedure developed in
our laboratory8 by condensation of benzil or p-methoxy-
benzil with one equivalent of an aromatic amine and acetic
acid in boiling ethanol (Scheme 3). As the success of the
reaction depends upon the nucleophilic properties of
the arylamine, the presence of electron-withdrawing sub-
stituents in ortho or para position was to be excluded.
Nevertheless, we were able to prepare in good yields a series
of differently substituted starting materials, most of them
bearing an electron-releasing group in para position
(Table 1).
2. Results and discussion
The preparation of benzil monoarylimines (1) was
Scheme 4.
Table 2. 2H-Benzo-1,4-thiazines 2 and benzothiazoles 3
Entry
Ar
R2
R4
Compd 2
mp (8C)a (Lit.)Ref.
Compd 3
mp (8C)a (Lit.)Ref.
Yield (%)
Yieldb (%)
a
b
c
e
f
g
h
k
l
C6H5
C6H5
C6H5
C6H5
C6H5
H
H
H
H
H
H
OCH3
H
H
H
Cl
H
CH3
OCH3
SCH3
N(CH3)2
OCH3
N(C2H5)2
N(CH3)2
N(C2H5)2
35
43
43
36
41
45
38
36
38
38
120±122
101±103 (100)16
123±126
68±71
±
±
67
79
72
71
64
77
59
67
73
111±112 (115±116)17,18
124±125 (124±126)18
111±113 (114±115)5b
112±114
115±118
151±153
139±141
137±140
89±92
C6H5
C6H5
130±131 (134±135)19
125±127
112±113
C6H5
p-CH3OC6H4
p-CH3OC6H4
142±144
113±115
m
114±116
a
Compounds 2, 3e±g, 3k±m: yellow crystals, compounds 3b, c, h: white crystals.
Yields based on starting compounds 2.
b

J.-D. Charrier et al. / Tetrahedron 57 62001) 4195±4202
4197
Scheme 5.
Table 3. Indoles 4
to afford unexpectedly either 2H-benzo-1,4-thiazines and
benzothiazoles or indoles.
Compd
R4
R5
Yield (%)
mp (8C)a (Lit.)Ref.
4d
4i
4j
H
OCH3
OCH3
H
H
OCH3
79
67
71
208±209 (203±204)20
199±200
219±220
In the cases of para or para and ortho substituted aromatic
amines, the reaction furnished predominantly 2H-benzo-
1,4-thiazines (2). We suggest the reaction to proceed
through the carbonyl sulfuration, followed by an intra-
molecular [412] cyclization involving both the thiazadienic
system and the aromatic ring, and achieved by a [1,5]-
proton shift (Scheme 4).
a
Compounds 4: white crystals.
Sulfuration of benzil phenylimine has already been investi-
gated by Hafez et al. in the 1980s'. The use of Lawesson's
reagent afforded 3,4,5-triphenyl-2-(4-methoxyphenyl)-
1,3,2-thiazaphosphole as a sole product instead of the
corresponding a-phenyliminothioketone.11 However, in a
following paper, phosphorus pentasul®de was reported to
successfully thionate 1,2-diphenyl-2-phenyliminoethanone
leading to 1,2-diphenyl-2-phenyliminoethanethione, the
latter being described as a stable compound.12
It must be pointed out that oxidation of 2 leading to
benzothiazoles (3) by ring contraction is certainly involved
during the workup procedure. Thus, the yields of 2 given in
Table 2 are somewhat underestimated. Indeed, the resulting
benzothiazines were found to be unstable when puri®ed by
column chromatography. However, once they have been
isolated, stability of 2 must be emphasized. It is also
noteworthy that the reaction can be completed at the
benzothiazole stage by heating overnight the corresponding
benzothiazines with silica without any solvent (Table 2).
These results are not surprising since it is well known that
exposing a 1,4-thiazine to oxidation leads easily to sulf-
oxides, which may then evolve towards thiazoles.13 We
suggest that oxidation of 2H-benzo-1,4-thiazines with
oxygen provides benzoylthiazolines in the same way,
which then undergo a ring contraction with concomitant
In contrast with the above result, we were not able to isolate
aryliminothioketones when reacting compounds 1 with
phosphorus pentasul®de. In fact, if thionation probably
occurred, the generation of the corresponding unstable
thioxo derivatives systematically underwent intramolecular
cyclization. Interestingly, a clear difference in reactivity
was found depending on the position and nature of the
substituents on the starting arylamine, inducing annulation
Scheme 6.

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J.-D. Charrier et al. / Tetrahedron 57 62001) 4195±4202
loss of benzaldehyde, giving rise to benzothiazoles (3)
(Scheme 5). The latest mechanism step has already
been proposed by Bayer et al.14 Furthermore, a slightly
different mechanism was recently reported by Puebla et
al., who have successfully carried out the dehydrogenation
of a 3,4-dihydro-2H-benzo-1,4-thiazine with DDQ in order
to con®rm its structure and observed the ring contraction of
the resulting benzothiazolium salt under basic conditions.15
Chemical shifts (d) are given in ppm down®eld from tetra-
methylsilane as internal standard. Mass spectra were
determined with a Hewlett Packard 5989 spectrometer.
The IR spectra were obtained using a BRUKER Vector 22
spectrometer.
All microanalyses were satisfactory (C ^0.3; H ^0.3; N
^0.3; S ^0.3).
Conversely, in the presence of an initial aromatic amine
bearing a meta methoxy group, the reaction occurred in
the same conditions to provide unequivocally indoles (4)
in high yields with total regioselectivity, as indicated in
Table 3. Although the mechanistic details of this reaction
remain unknown, we speculate that the benzil arylimine is
also ®rst converted to the a-aryliminothioketone. However,
in this case, the electron-donating effect of the 3-methoxy
substituent is strong enough to induce an intramolecular
conjugate addition regiospeci®cally at the 6-position of
the arylamine moiety rather than the [412] cyclization
path, thus yielding to 4 through an electrophilic substitution
followed by sulfur extrusion (Scheme 6). The indoles were
unambiguously characterized by spectroscopic data. The
1H NMR spectrum of 4i showed two singlets at d 6.91
and 7.09 due to the indolic protons and thus excluded the
4,5-dimethoxy structure.
4.2. Preparation of startingbenzil monoarylimines 1
To a solution of benzil (5 mmol) and acetic acid (5 mmol) in
ethanol (8 mL) was added the aromatic amine (5 mmol)
(7.5 mmol for 1a) at room temperature (for 1a, the reaction
Ê
was performed without acetic acid, but in toluene with 3 A
molecular sieves (2 g)). After stirring under re¯ux for 20 h,
the solvent was removed. The mixture was then diluted with
ethyl acetate, washed with a saturated solution of NH4Cl,
dried over MgSO4 and evaporated under vacuum. The crude
product was chromatographed (eluting with CH2Cl2 for 1g,
k, l, m; CH2Cl2/petroleum ether (4:1) for 1d, e, f, h, i, j;
CH2Cl2/petroleum ether (3:2) for 1a, b, c), affording
compounds 1, which were crystallized from ethanol (except
for 1j, which was isolated as an oil).
Physical and analytical data are presented in Tables 1 and 4.
So this last reaction allows to prepare a desulfurized
compound via the thionation of the stable carbonyl starting
material. Moreover our method offers a reliable alternative
to previous indolization routes20 such as Fischer cyclization,
since it provides exclusively one regioisomer in high yields.
4.3. Sulfuration of benzil monoarylimines. Preparation
of benzothiazines 2 and indoles 4
To a solution of benzil monoarylimine (1) (3 mmol) in
xylene (2a, b, c, e, f, h) or toluene (2g, k, l, m, 4)
(30 mL) was added portionwise P4S10 (0.9 mmol for 2a, b,
c, f, g, h; 1.2 mmol for 2e, k, l, m; 0.6 mmol for 4). The
reaction mixture was re¯uxed for 24 h for 2 or 4 h for 4.
Then it was cooled, ®ltered through a short pad of celite and
concentrated under reduced pressure. Puri®cation by ¯ash
chromatography (using as eluant CH2Cl2 for 2g, h, k, l, m;
CH2Cl2/petroleum ether (4:1) for 2e, f, 4; CH2Cl2/petroleum
ether (3:2) for 2a, b, c) afforded compounds 2 and 4, which
were crystallized from ether (2) or ethanol (4).
3. Conclusion
In summary, this study has shown powerfull new appli-
cations of 1-thia-4-azadienes, which have already provided
an easy access to 1,4-thiazines, thiazoles, thiazolines and
even to 1,3,4-thiadiazines.2 Interestingly, the synthetic
usefulness of this method is based on the possibility of
synthesizing either 2H-benzo-1,4-thiazines and benzo-
thiazoles or indoles by the opportune choice of the C-3
substituent on the initial arylamine. Further work exploiting
the potential of this approach applied to polysubstituted
heterocycles actually investigated in the laboratory will be
reported very soon.
Physical and analytical data are presented in Tables 3, 5 and
6.
4.4. Preparation of benzothiazoles 3
The benzothiazine (2) (1 mmol) was vigorously stirred at
1008C with silica (0.5 g) for 20 h. The mixture was cooled,
then diluted with CH2Cl2 and chromatographed (using as
eluent CH2Cl2 for 3b, c, e, f, h; CH2Cl2/ethyl acetate
(19:1) for 3g, k, l, m). Compounds 3 were crystallized
from ethanol.
4. Experimental
4.1. General
All reagents were purchased from Acros Organics and
Aldrich. The elemental analyses were performed by the
C.N.R.S. Analysis Laboratory (Vernaison). Column
chromatography was conducted on silica gel 60 (40±
63 mm), available from E. Merck. Thin layer chroma-
tography was performed on 0.5 mm£20 cm£20 cm E.
Merck silica gel plate (60 F-254). Melting points measured
using a Reichert microscope were uncorrected. The 13C and
1H NMR spectra were recorded at room temperature using
a BRUKER AC 200 at 50 and 200 MHz, respectively.
Physical and analytical data are presented in Tables 3 and 7.
Acknowledgements
The authors wish to express their gratitude to the French
Ministry of Education and CNRS for ®nancial support.

J.-D. Charrier et al. / Tetrahedron 57 62001) 4195±4202
4199
Table 4. Physical data for benzil arylimines 1
Compd
1H RMN (CDCl3) d, ppm
13C RMN (CDCl3) d, ppm
IR (KBr)a cm21
MS m/e (%)
1a
6.82, 7.09 (2d, Jˆ8.5 Hz, 4
H-Ar), 7.32±7.55 (m, 6 H-Ar),
7.73±7.89 (m, 4 H-Ar)
122.0, 123.3, 128.9, 129.0,
129.1, 129.5, 132.1, 134.7 (14
CH-Ar), 130.2, 134.7, 135.0,
147.9 (4 C-Ar), 167.1 (CyN),
197.4 (CyO)
120.6, 124.8, 128.3, 128.8,
129.0, 129.4, 131.8, 134.4 (15
CH-Ar), 134.9, 135.3, 149.4 (3
C-Ar), 166.4 (CyN), 197.8
(CyO)
21.0 (CH3), 120.7, 128.2, 128.9,
129.0, 129.4, 129.5, 131.7, 134.4
(14 CH-Ar), 134.5, 134.8, 135.5,
146.8 (4 C-Ar), 166.0 (CyN),
198.2 (CyO)
55.3 (OCH3), 106.1, 111.1, 113.1
128.3, 129.1 129.5, 129.6, 131.9,
134.4 (14 CH-Ar), 135.0, 135.2,
150.6, 159.9 (4 C-Ar), 166.5
(CyN), 197.6 (CyO)
55.2 (OCH3), 113.9, 122.2,
127.9, 128.7, 128.8, 129.2,
131.4, 134.3 (14 CH-Ar), 134.5,
135.3, 142.3, 157.0 (4 C-Ar),
165.3 (CyN), 198.6 (CyO)
16.4 (SCH3), 121.5, 127.4,
128.2, 129.0, 129.0, 129.2,
129.4, 130.1 (14 CH-Ar), 131.8,
134.6, 135.0, 146.8 (4 C-Ar),
166.3 (CyN), 198.0 (CyO)
40.5 (N(CH3)2), 112.4, 122.9,
127.7 128.6, 128.8, 129.2, 130.8,
134.1 (14 CH-Ar), 134.5, 135.9,
138.4, 148.4 (4 C-Ar), 162.9
(CyN), 199.8 (CyO)
55.4 (2 OCH3), 99.3, 103.6,
121.5, 128.3, 128.6, 128.8,
129.1, 131.5, 134.2 (13 CH-Ar),
132.4, 134.7, 135.5, 151.4, 158.3
(5 C-Ar), 166.5 (CyN), 197.9
(CyO)
55.8, 56.0 (2 OCH3), 105.7,
111.2, 113.0, 128.1, 128.9,
129.0, 129.3, 131.6, 134.4 (13
CH-Ar), 134.8, 135.4, 142.8,
146.6, 148.9 (5 C-Ar), 165.8
(CyN), 198.8 (CyO)
55.8 (2 OCH3), 60.7 (OCH3),
98.5, 128.0, 128.7, 129.1, 131.6,
134.2 (12 CH-Ar), 134.9, 135.0,
145.1, 153.0 (6 C-Ar), 166.4
(CyN), 198.1 (CyO)
12.5 (2 CH3), 44.4 (2 NCH2),
111.9, 123.5, 127.7 128.6, 128.8,
129.3, 130.7, 134.0 (14 CH-Ar),
134.8, 136.1, 137.5, 146.0 (4
C-Ar), 162.1 (CyN), 200.2
(CyO)
40.7 (N(CH3)2), 55.5, 55.6 (2
OCH3), 112.7, 114.1, 114.2
122.9, 129.6, 131.9 (12 CH-Ar),
128.0, 129.0, 139.1, 148.3,
161.9, 164.3 (6 C-Ar), 163.0
(CyN), 198.2 (CyO)
12.6 (2 CH3), 44.5 (2 NCH2),
55.4, 55.5 (2 OCH3), 112.2,
114.1, 114.2 123.4, 129.5, 131.9
(12 CH-Ar), 128.1, 129.2, 138.1,
145.8, 161.8, 164.3 (6 C-Ar),
162.2 (CyN), 198.6 (CyO)
1664, 1624, 1477, 1192, 906,
836, 690, 666
321/319 (1/3, M1´), 217/215
(10/32), 216/214 (70/100),
113/111 (16/51), 77 (32), 75
(37), 51 (13)
1b
1c
1d
1e
1f
6.86±6.95 (m, 3H-Ar), 7.08±
7.16 (m, 2 H-Ar), 7.27±7.52 (m,
6 H-Ar), 7.73±7.91 (m, 4 H-Ar)
1667, 1622, 1591, 1576, 695,
687
285 (4, M1´), 181 (22), 180
(100), 77 (53), 51 (22)
2.17 (s, 3H, CH3), 6.80, 6.93 (2d,
Jˆ8.1 Hz, 4H-Ar), 7.29±7.51
(m, 6 H-Ar), 7.75±7.89
(m, 4 H-Ar)
1664, 1619, 1575, 1446, 1226,
1193, 1169, 698
299 (6, M1´), 195 (37), 194
(100), 91 (55), 77 (18), 65 (43)
3.65 (s, 3H, OCH3), 6.44±6.49
(m, 3H-Ar), 7.01 (t, Jˆ8.0 Hz, 1
H-Ar), 7.34±7.49 (m, 6H-Ar),
7.75±7.89 (m, 4H-Ar)
1601, 1577, 1140, 692
1669, 1501, 1289, 1240
315 (2, M1´), 211 (15), 210
(100), 107 (10), 92 (20), 77 (30)
3.68 (s, 3H, OCH3), 6.66, 6.89
(2d, Jˆ8.7 Hz, 4H-Ar), 7.26±
7.51 (m, 6 H-Ar), 7.75±7.88
(m, 4 H-Ar)
315 (5, M1´), 211 (15), 210
(100), 92 (13), 77 (23)
2.36 (s, 3H, SCH3), 6.84, 7.04
(2d, Jˆ8.7 Hz, 4H-Ar), 7.28±
7.56 (m, 6 H-Ar), 7.72±8.00
(m, 4 H-Ar)
1674, 1576, 1475, 1447, 1231,
1196, 826, 697, 691
331 (11, M1´), 227 (18), 226
(100), 77 (8)
1g
1h
2.83 (s, 6H, N(CH3)2), 6.50, 6.93
(2d, Jˆ8.9 Hz, 4H-Ar), 7.25±
7.50 (m, 6 H-Ar), 7.76±7.89
(m, 4 H-Ar)
1666, 1511, 820, 700, 690
328 (13, M1´), 224 (16), 223
(100), 105 (7), 77 (11)
3.65, 3.68 (2s, 6H, 2 OCH3), 6.23
(d, Jˆ9.4 Hz, 1H-Ar), 6.26 (s,
1H-Ar), 6.68 (d, Jˆ9.4 Hz,
1H-Ar), 7.25±7.50 (m, 6 H-Ar),
7.79±7.89 (m, 4 H-Ar)
1666, 1608, 1599, 1499, 1209,
1190, 1157, 1129
345 (6, M1´), 241 (16), 240
(100), 210 (8), 77 (7)
1i
3.72, 3.75 (2s, 6H, 2 OCH3), 6.50
(dd, Jˆ8.4 Hz, Jˆ2.3 Hz, 1
H-Ar), 6.55 (d, Jˆ2.3 Hz, 1
H-Ar), 6.63 (d, Jˆ8.4 Hz, 1
H-Ar), 7.29±7.53 (m, 1H-Ar),
7.74±7.80 (m, 4H-Ar)
3.66 (s, 6H, 2 OCH3), 3.70 (s,
3H, OCH3), 6.16 (s, 2 H-Ar),
7.31±7.55 (m, 6H-Ar), 7.76±
7.90 (m, 4H-Ar)
1668, 1507, 1258, 1237, 1134,
1022
345 (6, M1´), 241 (16), 240
(100), 122 (12), 79 (17), 77 (18),
51 (11)
1j
1671, 1583, 1502, 1448, 1222,
1177, 1119, 1007, 690
375 (22, M1´), 271 (20), 270
(100), 109 (12), 105 (48), 81
(13), 77 (69), 66 (15), 51 (23)
1k
1.05 (t, Jˆ7.1 Hz, 6H, 2 CH3),
3.23 (q, Jˆ7.1 Hz, 4H, 2 NCH2),
6.45, 6.94 (2d, Jˆ9.0 Hz,
1663, 1612, 1511, 1269, 1207,
818, 697, 682
356 (18, M1´), 252 (18), 251
(100), 77 (12)
4H-Ar), 7.30±7.51 (m, 6 H-Ar),
7.78±7.85 (m, 4 H-Ar)
1l
2.82 (s, 6H, N(CH3)2), 3.77, 3.81
(2s, 6H, 2 OCH3), 6.51, 6.93 (2d,
Jˆ8.9 Hz, 4H-Ar), 6.79, 7.76
(2d, Jˆ8.8 Hz, 4H-Ar), 6.89,
7.80 (2d, Jˆ8.9 Hz, 4H-Ar)
1601, 1599, 1515, 1259, 1173
1594, 1515, 1268, 1174, 1161
388 (7, M1´), 254 (18), 253
(100), 169 (10), 149 (14), 105
(10), 77 (17)
1m
1.06 (t, Jˆ7.1 Hz, 6H, 2 CH3),
3.24 (q, Jˆ7.1 Hz, 4H, 2 NCH2),
3.79, 3.82 (2s, 6H, 2 OCH3),
6.46, 6.92 (2d, Jˆ9.0 Hz,
4H-Ar), 6.80, 7.78 (2d,
416 (14, M1´), 282 (20), 281
(100), 237 (7), 133 (8)
Jˆ9.0 Hz, 4H-Ar), 6.89, 7.78
(2d, Jˆ8.9 Hz, 4H-Ar)
a
Except for 1j: ®lm.

4200
J.-D. Charrier et al. / Tetrahedron 57 62001) 4195±4202
Table 5. Physical data for 2H-benzo-1,4-thiazines 2
Compd
1H RMN (CDCl3) d, ppm
13C RMN (CDCl3) d, ppm
IR (KBr) cm21
MS m/e (%)
2a
5.25 (s, 1H, CH), 7.13±7.26
(m, 7 H-Ar), 7.37±7.46 (m, 3
H-Ar), 7.50 (d, Jˆ8.9 Hz,
1 H-Ar), 7.92±8.01
38.9 (CH), 127.0, 127.3, 127.4,
127.7, 128.2, 128.9, 129.0, 129.3,
131.2 (13 CH-Ar), 121.7, 132.7,
137.3, 138.0, 141.6 (5 C-Ar), 157.5
(CyN)
34.4 (CH), 123.4, 125.4, 126.6,
127.8, 128.6, 129.2, 129.2, 130.1,
130.4 (14 CH-Ar), 121.8, 131.2,
133.8, 135.2
1594, 1449, 1446,
726, 693, 688
337/335 (30/78, M1´), 336/334
(53/100), 260/258 (6/15), 178 (14),
165 (10)
(m, 2 H-Ar)
5.24 (s, 1H, CH), 7.10
2b
2c
2e
_
301 (83, M1´), 300 (100), 224 (19),
223 (10), 197 (12), 178 (12), 165
(23), 121 (13), 77 (11)
(t, Jˆ7.5 Hz, 1 H-Ar),
7.16±7.24 (m, 7 H-Ar),
7.42±7.44 (m, 3 H-Ar), 7.59 (d,
Jˆ7.9 Hz, 1 H-Ar), 7.97±8.00
(m, 2 H-Ar)
(4 C-Ar), 154.2 (CyN)
2.26 (s, 3H, CH3), 5.20 (s, 1H,
CH), 7.03 (s, 1 H-Ar), 7.05 (d,
Jˆ7.9 Hz, 1 H-Ar), 7.16±7.21
(m, 5 H-Ar), 7.40±7.41 (m, 3
H-Ar), 7.46 (d, Jˆ7.9 Hz, 1
H-Ar), 7.95±7.97 (m, 2 H-Ar)
3.75 (s, 3H, OCH3), 5.20
(s, 1H, CH), 6.70 (d, Jˆ2.8 Hz,
1 H-Ar), 6.78 (dd, Jˆ8.7 Hz,
Jˆ2.8 Hz, 1 H-Ar), 7.19±7.25
(m, 5 H-Ar), 7.39±7.42 (m,
3 H-Ar), 7.51 (d, Jˆ8.7 Hz,
1 H-Ar), 7.92±7.97
21.3 (CH3), 39.3 (CH), 127.4, 127.6,
127.8, 128.0, 128.1, 128.2, 128.8,
128.9, 130.7 (13 CH-Ar), 119.3,
137.6, 138.1, 138.5, 141.0 (5 C-Ar),
156.2 (CyN)
1606, 1446, 817,
764, 724, 693, 690
315 (74, M1´), 314 (100), 238 (18),
178 (12), 165 (13)
39.3 (CH), 55.6 (OCH3), 112.0,
113.3, 127.4, 128.0, 128.8, 128.9,
129.7, 130.5 (13 CH-Ar), 121.0,
137.3, 138.2, 138.5, 158.7 (5 C-Ar),
154.7 (CyN)
1679, 1603, 1226,
1211, 826, 684
331 (68, M1´), 330 (100), 254 (11)
(m, 2 H-Ar)
2.44 (s, 3H, SCH3), 5.24 (s, 1H,
CH), 7.03 (d, Jˆ2.1 Hz,
2f
15.7 (SCH3), 39.2 (CH), 124.5, 124.7,
127.4, 127.6, 128.1, 128.6, 128.8,
129.0, 130.81 (13 CH-Ar), 120.7,
137.8, 138.1, 138.3, 140.5 (5 C-Ar),
156.2 (CyN)
1681, 1477, 1049,
1035, 824, 758,
683
347 (88, M1´), 346 (100), 331 (12),
270 (18), 184 (10), 178 (13), 122
(29), 121 (19)
1 H-Ar), 7.09 (dd, Jˆ8.3 Hz,
Jˆ2.1 Hz, 1 H-Ar), 7.11±7.19
(m, 5 H-Ar), 7.39±7.45 (m, 3
H-Ar), 7.49 (d, Jˆ8.3 Hz, 1
H-Ar), 7.93±8.00 (m, 2 H-Ar)
2.92 (s, 6H, N(CH3)2), 5.17 (s,
1H, CH), 6.43 (d, Jˆ2.8 Hz, 1
H-Ar), 6.58 (dd, Jˆ8.7 Hz,
Jˆ2.8 Hz, 1 H-Ar), 7.15±7.24
(m, 5 H-Ar), 7.35±7.39 (m, 3
H-Ar), 7.45 (d, Jˆ8.7 Hz, 1
H-Ar), 7.89±7.94 (m, 2 H-Ar)
3.74, 3.94 (2s, 6H, 2 OCH3),
5.22 (s, 1H, CH), 6.31 (d,
Jˆ2.4 Hz, 1 H-Ar), 6.34 (d,
Jˆ2.4 Hz, 1 H-Ar), 7.14±7.29
(m, 5 H-Ar), 7.34±7.44 (m, 3
H-Ar), 7.91±8.00 (m, 2 H-Ar)
1.13 (t, Jˆ7.1 Hz, 6H, 2 CH3),
3.30 (q, Jˆ7.1 Hz, 4H, 2
NCH2), 5.16 (s, 1H, CH), 6.37
(d, Jˆ2.9 Hz, 1 H-Ar), 6.54
(dd, Jˆ9.0 Hz, Jˆ2.9 Hz, 1
H-Ar), 7.17±7.29 (m, 5 H-Ar),
7.33±7.40 (m, 3 H-Ar), 7.54 (d,
Jˆ9.0 Hz, 1 H-Ar), 7.88±7.93
(m, 2 H-Ar)
2g
39.9 (CH), 40.4 (N(CH3)2), 110.0,
110.9, 127.1, 127.4, 127.8, 128.7,
128.9, 129.8, 129.9 (13 CH-Ar),
120.7, 133.9, 138.9, 139.0, 149.7
(5 C-Ar), 152.1 (CyN)
1607, 1576, 1551,
1442, 1368
344 (100, M1´), 343 (93), 267 (18)
2h
2k
39.0 (CH), 55.6, 56.4 (2 OCH3), 98.0,
102.7, 127.4, 127.6, 127.9, 128.7,
128.8, 130.3 (12 CH-Ar), 122.0,
127.8, 137.9, 138.8, 152.7, 159.2
(6 C-Ar), 156.7 (CyN)
1597, 1558, 1313,
1150, 1060, 695
361 (100, M1´), 360 (77), 346 (15),
284 (7), 270 (40)
12.7 (2 CH3), 39.9 (CH), 44.4
(2 NCH2), 109.0, 110.1, 126.9, 127.3,
127.6, 128.5, 128.8, 129.7, 130.0
(13 CH-Ar), 120.8, 133.0, 138.9,
139.1, 147.2 (5 C-Ar), 151.1 (CyN)
1608, 1493, 1352,
1197, 695
372 (100, M1´), 371 (75), 358 (16),
357 (60), 328 (10), 327 (18)
2l
2.89 (s, 6H, N(CH3)2), 3.66,
3.79 (2s, 6H, 2 OCH3), 5.12 (s,
1H, CH), 6.43 (d, Jˆ2.5 Hz, 1
H-Ar), 6.57 (dd, Jˆ8.9 Hz,
Jˆ2.5 Hz, 1 H-Ar), 6.68, 7.12
(2d, Jˆ8.5 Hz, 4 H-Ar), 6.88,
7.88 (2d, Jˆ8.7 Hz, 4 H-Ar),
7.42 (d, Jˆ8.9 Hz, 1 H-Ar)
1.13 (t, Jˆ6.9 Hz, 6H, 2 CH3),
3.30 (q, Jˆ6.9 Hz, 4H, 2
NCH2), 3.70, 3.81 (2s, 6H, 2
OCH3), 5.11 (s, 1H, CH), 6.38
(d, Jˆ2.1 Hz, 1 H-Ar), 6.54
(dd, Jˆ8.8 Hz, Jˆ2.1 Hz, 1
H-Ar), 6.71, 7.14 (2d,
39.2 (CH), 40.5 (N(CH3)2), 55.2, 55.5
(2 OCH3), 110.2, 110.9, 114.0, 114.3,
128.5, 128.7, 129.4 (11
CH-Ar), 120.5, 130.9, 131.5, 134.0,
149.4, 159.1, 161.1 (7 C-Ar),
152.1 (CyN)
1604, 1509, 1254,
1172, 834
404 (100, M1´), 403 (57), 389 (29)
2m
12.8 (2 CH3), 39.4 (CH), 44.4
(2 NCH2), 55.2, 55.5 (2 OCH3),
109.3, 110.2, 114.0, 114.2, 128.6,
129.7 (11 CH-Ar), 120.7, 131.1,
131.6, 133.2, 147.0, 159.1, 161.0
(7 C-Ar), 151.2 (CyN)
1599, 1508, 1259,
830, 783
432 (100, M1´), 431 (54), 418 (27),
417 (96), 373 (10), 227 (10), 216
(13), 208 (14), 132 (12)
Jˆ8.5 Hz, 4 H-Ar), 6.88, 7.86
(2d, Jˆ8.8 Hz, 4 H-Ar), 7.39
(d, Jˆ8.8 Hz, 1 H-Ar)

J.-D. Charrier et al. / Tetrahedron 57 62001) 4195±4202
4201
Table 6. Physical data for benzothiazoles 3
Compd
1H RMN (CDCl3) d, ppm
13C RMN (CDCl3) d, ppm
IR (KBr) cm21
MS m/e (%)
3b
7.37 (td, Jˆ7.6 Hz, Jˆ1.2 Hz,
1 H-Ar), 7.46±7.50 (m, 4 H-Ar),
7.88 (ddd, Jˆ8.1 Hz, Jˆ1.2 Hz,
Jˆ0.6 Hz, 1 H-Ar), 8.06±8.11
(m, 3 H-Ar)
121.8, 123.4, 125.3, 126.5,
127.7, 129.2, 131.1
(9 CH-Ar), 133.8, 135.2,
154.3 (3 C-Ar), 168.2 (CyN)
1479, 963, 767, 687
212 (15, (M11)1´), 211 (100, M1´),
108 (23), 69 (16)
3c
3e
3f
2.49 (s, 3H, CH3), 7.29 (dd,
Jˆ8.2 Hz, Jˆ1.2 Hz, 1 H-Ar),
7.45±7.49 (m, 3 H-Ar), 7.68
(m, 1 H-Ar), 7.94 (d, Jˆ8.2 Hz,
1 H-Ar), 8.04±8.09 (m, 2 H-Ar)
3.85 (s, 3H, OCH3), 7.07 (dd,
Jˆ8.9 Hz, Jˆ2.6 Hz, 1 H-Ar), 7.31
(d, Jˆ2.6 Hz, 1 H-Ar), 7.42±7.50
(m, 3 H-Ar), 7.94 (d, Jˆ8.9 Hz,
1 H-Ar), 8.00±8.04 (m, 2 H-Ar)
2.55 (s, 3H, SCH3), 7.38 (dd,
Jˆ8.6 Hz, Jˆ1.9 Hz, 1 H-Ar),
7.43±7.50 (m, 3 H-Ar) 7.73
(d, Jˆ1.9 Hz, 1 H-Ar), 7.94
(d, Jˆ8.6 Hz, 1 H-Ar), 8.00±8.08
(m, 2 H-Ar)
3.02 (s, 6H, N(CH3)2), 6.96 (dd,
Jˆ9.1 Hz, Jˆ2.5 Hz, 1 H-Ar), 7.11
(d, Jˆ2.5 Hz, 1 H-Ar), 7.43±7.50
(m, 3 H-Ar), 7.90 (d, Jˆ9.1 Hz,
1 H-Ar), 8.00±8.04 (m, 2 H-Ar)
3.86, 4.03 (2s, 6H, 2 OCH3), 6.54
(d, Jˆ1.8 Hz, 1 H-Ar), 6.91
(d, Jˆ1.8 Hz, 1 H-Ar) 7.41±7.44
(m, 3 H-Ar), 8.04±8.08 (m, 2 H-Ar)
21.5 (CH3), 121.3, 122.7,
127.4, 127.9, 128.9, 130.7
(8 CH-Ar), 133.7, 135.2,
135.3, 152.2 (4 C-Ar),
167.0 (CyN)
55.9 (OCH3), 104.2, 115.8,
123.8, 127.3, 129.1, 130.7
(8 CH-Ar), 133.9, 136.5,
148.8, 157.9 (4 C-Ar),
165.7 (CyN)
16.8 (SCH3), 119.1, 123.4,
126.1, 127.6, 129.2, 131.1
(8 CH-Ar), 133.7, 136.1,
136.3, 152.3 (4 C-Ar),
167.3 (CyN)
1480, 816, 768, 690
226 (28, (M11)1´), 225 (100, M1´),
122 (26), 121 (40), 112 (13), 78 (16),
77 (23)
1483, 1265, 1226,
829
242 (26, (M11)1´), 241 (100, M1´),
227 (13), 226 (84), 198 (34), 95 (31)
1478, 1259, 812,
758, 684
258 (29, (M11)1´), 257 (100, M1´),
243 (11), 242 (72), 139 (18), 95 (15)
3g
3h
3k
41.0 (N(CH3)2), 103.0, 113.5,
123.3, 127.1, 128.9, 130.1
(8 CH-Ar), 134.2, 137.3,
146.2, 148.9 (4 C-Ar),
163.1 (CyN)
55.9, 56.2 (2 OCH3), 95.3,
98.1, 127.4, 128.9, 130.4
(7 CH-Ar), 133.8, 137.6,
139.5, 154.0, 159.1 (5 C-Ar),
164.2 (CyN)
12.7 (2 CH3), 45.1 (2 NCH2),
102.3, 113.1, 123.7, 127.2,
129.1, 130.1 (8 CH-Ar),
134.3, 137.7, 145.7, 146.4
(4 C-Ar), 162.6 (CyN)
1604, 1593, 1574,
1507, 1440, 1354,
956, 687
255 (27, (M11)1´), 254 (100, M1´),
253 (56), 239 (13), 238 (15)
1574, 1271, 1212,
1151
272 (29, (M11)1´), 271 (100, M1´),
270 (74), 242 (52), 241 (28), 228 (11),
227 (11), 226 (14), 213 (12), 121 (26),
82 (11), 69 (10)
1.22 (t, Jˆ7.1 Hz, 6H, 2 CH3), 3.43
(q, Jˆ7.1 Hz, 4H, 2 NCH2), 6.90
(dd, Jˆ9.0 Hz, Jˆ2.2 Hz, 1 H-Ar),
7.06 (d, Jˆ2.2 Hz, 1 H-Ar)
7.37±7.52 (m, 3 H-Ar), 7.86
(d, Jˆ9.0 Hz, 1 H-Ar), 7.96±8.08
(m, 2 H-Ar)
1592, 1543, 1509,
1468, 1354, 1273
283 (11, (M11)1´), 282 (45, M1´), 268
(18), 267 (100), 239 (24), 238 (17), 211
(15), 210 (13)
3l
3.03 (s, 6H, N(CH3)2), 3.85 (s, 3H,
OCH3), 7.04 (dd, Jˆ9.0 Hz,
Jˆ2.4 Hz, 1 H-Ar), 7.30
41.4 (N(CH3)2), 55.6 (OCH3),
103.6, 113.6, 114.4, 123.0,
128.7 (7 CH-Ar), 127.1,
131.9, 137.1, 146.6, 148.5
(5 C-Ar), 161.4 (CyN)
1607, 1483, 1251,
1174
285 (27, (M11)1´), 284 (100, M1´),
283 (17), 270 (10), 269 (50), 241 (10),
142 (17)
(d, Jˆ2.4 Hz, 1 H-Ar), 7.89
(d, Jˆ9.0 Hz, 1 H-Ar), 6.96, 7.95
(2d, Jˆ8.9 Hz, 4 H-Ar)
3m
1.20 (t, Jˆ7.1 Hz, 6H, 2 CH3), 3.41
(q, Jˆ7.1 Hz, 4H, 2 NCH2), 3.85
(s, 3H, OCH3), 6.88 (dd, Jˆ9.0 Hz,
Jˆ2.5 Hz, 1 H-Ar), 7.05
12.5 (2 CH3), 45.3 (2 NCH2),
55.6 (OCH3), 103.8, 113.8,
114.4, 123.3, 128.7
(7 CH-Ar), 127.1, 131.9,
137.4, 145.6, 146.0 (5 C-Ar),
161.5 (CyN)
1608, 1465, 1252,
1170
313 (16, (M11)1´), 312 (58, M1´), 298
(21), 297 (100), 269 (15), 268 (21), 253
(10), 135 (33)
(d, Jˆ2.5 Hz, 1 H-Ar), 7.82
(d, Jˆ9.0 Hz, 1 H-Ar), 6.96, 7.94
(2d, Jˆ8.7 Hz, 4 H-Ar)
Table 7. Physical data for indoles 4
Compd
1H RMN d, ppma
13C RMN d, ppma
IR (KBr) cm21
MS m/e (%)
4d
3.82 (s, 3H, OCH3), 6.75 (dd,
Jˆ8.9 Hz, Jˆ2.3 Hz, 1 H-Ar),
7.00 (d, Jˆ2.3 Hz, 1 H-Ar),
55.7 (OCH3), 95.2, 110.9, 120.5, 3338, 1260, 1196, 1158, 1122, 697 299 (100, M1´), 285 (14), 284 (68), 257
126.9, 127.9, 128.8, 129.3, 129.3,
130.8 (13 CH-Ar), 115.0, 124.0 (2
(10), 254 (11)
7.18±7.51 (m, 11 H-Ar), 10.40 CyC), 133.8, 134.0, 136.7, 138.2,
(br s, 1H, NH)
157.8 (5 C-Ar)
4i
4j
3.87, 3.91 (2s, 6H, 2 OCH3), 6.91, 56.3, 56.6 (2 OCH3), 94.6, 101.5, 3407, 1491, 1474, 1465, 1338,
7.09 (2s, 2 H-Ar), 7.25±7.45 (m, 126.3, 127.3, 127.9, 128.7, 128.8, 1244, 1193, 1145, 702, 699
329 (100, M1´), 315 (11), 314 (49), 286
(20), 148 (11), 120 (10)
10 H-Ar), 8.14 (br s, 1H, NH)
130.2 (12 CH-Ar), 115.1, 121.9 (2
CyC), 130.6, 132.9, 133.1, 136.6,
145.8, 147.7 (6 C-Ar)
3.30, 3.69, 3.83 (3s, 9H, 3 OCH3), 56.9, 60.5, 60.8 (3 OCH3), 90.4,
6.77 (s, 1 H-Ar), 7.18±7.34 (m, 126.0, 126.7, 127.4, 127.6, 128.2,
10 H-Ar), 11.36 (br s, 1H, NH) 130.9 (11 CH-Ar), 113.2, 115.4 (2
CyC), 132.5, 132.6, 133.0, 136.2,
3363, 1498, 1293, 1106, 696
359 (100, M1´), 345 (10), 344 (37), 301
(21), 286 (21), 230 (17), 164 (18)
136.4, 146.3, 150.6 (7 C-Ar)
a
Spectra were recorded in Acetone d6 for 4d, CDCl3 for 4i, DMSO d6 for 4j.

4202
J.-D. Charrier et al. / Tetrahedron 57 62001) 4195±4202
2000, 695±702. (b) Landreau, C.; Deniaud, D.; Reliquet, A.;
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