Regioselective one pot synthesis of 2-alkyl/aryl-4H-benzo[1,4]thiazine-3- one via microwave irradiation

Article abstract of DOI:10.1002/jhet.5570430632

A series of 2-alkyl/aryl-4H-benzo[1,4]thiazine-3-ones have been synthesized by microwave irradiation of ethyl-2-bromo-2-alkyl/aryl acetate and 2-amino thiophenol in the presence of 1,8-diazabicyclo-[5.4.0]undec-7-ene and N-methylpiperidine. All compounds were characterized by ¹H NMR, ¹³C NMR and elemental analyses, and by X-ray crystallography in the case of 2-methyl-4H-benzo[1,4]thiazin-3-one.

Full text of DOI:10.1002/jhet.5570430632

Nov-Dec 2006
1641
Regioselective One Pot Synthesis of 2-Alkyl/Aryl-4H-
benzo[1,4]thiazine-3-one via Microwave Irradiation
Sukanta Kamila, Benjamin Koh, Omair Khan, Hongming Zhang, Edward R. Biehl*
Department of Chemistry, Southern Methodist University, Dallas, TX 75275, USA
ebiehl@smu.edu
Received April 19, 2006
H
N
R2
O
R1
S
N
SH
Br
R2
O
=
CH3
4
DBU
R1
MW, 180°C, 4 minutes, 150W
S
R2
NH2
EtO
R1
R2 = alkyl/aryl group
R1 = H, Cl
N
O
1
2
H
95 - 98 %
(3a - 3h)
A series of 2-alkyl/aryl-4H-benzo[1,4]thiazine-3-ones have been synthesized by microwave irradiation
of ethyl-2-bromo-2-alkyl/aryl acetate and 2-amino thiophenol in the presence of 1,8-diazabicyclo-
[5.4.0]undec-7-ene and N-methylpiperidine. All compounds were characterized by 1H NMR, 13C NMR and
elemental analyses, and by X-ray crystallography in the case of 2-methyl-4H-benzo[1,4]thiazin-3-one.
J. Heterocyclic Chem., 43, 1641 (2006).
Introduction.
requiring 2 or more steps. These derivatives can also be
obtained by cyclization of alkyl 2-haloacetamidophenyl
sulphides [4a] or reductive cyclization of ꢀ-(o-nitro-
phenylthio)-carboxylic acids with aid of sodium boro-
hydride and palladium on charcoal [4b]. However,
neither of these starting material is commercially
available. Although many methods for the preparation of
2-alkyl-4H-benzo[1,4]thiazine-3-ones are available, very
few studies on this type of molecule are known [5].
Herein we describe a new high yield, one pot regio-
selective synthesis of 2-alkyl-4H-benzo[1,4]thiazine-3-
ones by microwave irradiation.
2-Alkyl-4H-benzo[1,4]thiazine-3-one derivatives have
attracted much interest due to their biological functions
[1]. For example, they can be used as effective tran-
quilizers [1b], angiotensin converting enzyme inhibitors
[1c], or aldose reductase inhibitors [1d], and some
[1,4]benzothiazines show anticancer activities [2]. These
compounds are also attractive targets for library
development because their structure contains multiple
positions for facile derivatization and/or modification.
The previous synthetic methods gave benzo[1,4]thi-
azine-3-ones in modest yields and required complication
procedures and prolong heating [1-4]. For example,
benzo[1,4]thiazine-3-ones were produced in 36-89%
yields by heating o-aminothiophenols or o-aminophenyl
disulphide in refluxing benzene until azeotropic distil-
lation was complete (~30 minutes) and then at 137-142
°C for 1 hour [1]. Recently, 4H-benzo[1,4]thiazine-3-ones
were prepared in 51-71% by a solid-phase synthesis
Results and Discussion.
2-Alkyl/aryl-4H-benzo[1,4]thiazine-3-ones (3) were
prepared by the microwave irradiation of a mixture of 2-
aminothiophenol (1) with a variety of ethyl-2-bromo-2-
alkyl/aryl acetate (2) in presence of 1.1 equiv of 1,8-
diazabicyclo[5.4.0]undec-7-ene and N-methylpiperidine
Scheme 1
H
N
R2
O
R1
S
N
SH
Br
R2
O
4
CH3
=
DBU
R1
MW, 180 °C, 4 minutes, 150W
S
R2
NH2
EtO
R
2 = alkyl/aryl group
R
1 = H, Cl
R1
1
2
N
O
H
95 - 98 %
(3a - 3h)

1642
S. Kamila, B. Koh, O. Khan, H.M. Zhang, E.R. Biehl
Vol 43
as solvent (Scheme 1). The yields are very good to
excellent (Table 2). As expected, in the absence of a base,
the desired 2-alkyl-4H-benzo[1,4]thiazine-3-ones were
not produced. Surprisingly, 3-alkyl-3,4-dihydrobenzo-
[1,4]thiazine-2-ones (4) were not obtained as evident from
the NMR and X-Ray crystallography.
Assuming that a base might help to remove the thiol
proton, we treated 2-amino thiophenol and ethyl 2-bromo
propionate (2a) with several bases and irradiated the
mixture for 4 min at 180 °C. The results are shown in
Table 1.
varying the amount of 1,8-diazabicyclo[5.4.0]undec-7-
ene, temperature or reaction time. In fact, when the
reaction mixture was heated above 200 °C for 4 minutes
or longer times, intractable mixtures were obtained.
Therefore, we selected the reaction conditions as 1: 2: 1,8-
diazabicyclo[5.4.0]undec-7-ene = 1.1: 1.0: 1.1, N-methyl
piperidine, 180 °C, 4-minutes.
A plausible mechanism shown in Figure 1 involves
nucleophilic attack by the –Sꢀ at the halogenated carbon
(rather than the carbonyl carbon) forming intermediate 5.
Compound 5 then undergoes intramolecular nucleophilic
addition by the amino group on to the carbonyl carbon of
the ester occurs to form a tetrahedral intermediate 6 which
after elimination of EtOH affords compound 3.
Table 1
Effect of base and solvent on the yields of 3a
Yield
of 3a
<10%
<20%
<5%
For comparison, we repeated the reaction of 1 and 2a
under conventional oil bath heating at 180 °C for 4
minutes. Compound 3a was obtained in only 40% yield
which is much lower than that (98%) obtained by
microwave irradiation. The difference in yields probably
reflects the difference between rapid and volumetric
microwave heating and slow superficial conventional
heating.
We next explored the scope of the one pot
synthesis of 2-methyl-4H-benzo[1,4]thiazine-3-one
(3a) under controlled microwave heating at 180 °C
for 4 minutes using a variety of commercially
available substituted 2-aminothiophenols (1) and 2.
The results, which are summarized in Table 2, show
that the yields of 3 ranged from 91-98% (except
entry 11 and 12). In case of 2-aryl group, the
nucleophilicity at the benzylic position is diminished
by the conjugation of the aromatic ring and thereby
decreasing the yield. The reaction procedure is
relatively simple: one adds compound 1, 2, and 3 to
N-methylpiperidine (2 mL) in a microwave test tube
and then irradiates the mixture with 150 psi pressure
and at 180 °C for 4 minutes. The reaction can be
scaled up without any diminution in yield. For
example, 3 g of compound 3a was prepared in 98%
in a one batch reaction.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Pyridine (1.1 equiv) DMF
EtN(i-prop)2 (1.1 equiv), DMF
EtN(i-prop)2 (1.1 equiv), N-methyl-pyrrolidone
Et3N (1.1 equiv), N- methylpyrrolidone
N-Methylpiperidine (1.1 equiv), DMF
No base, N- methylpyrrolidone
N-Methylpiperidine (1.1 equiv)
K2CO3 1.1 equiv), DMF
<30%
<20%
Trace
Trace
Trace
Trace
25%
N- Methylpyrrolidone (1.1 equiv)
1,8-Diazabicyclo[5.4.0]undec-7-ene (1.1 equiv),
DMF
11.
12.
13.
14.
1,8-Diazabicyclo[5.4.0]undec-7-ene 7-ene (2
equiv), DMF
20%
~70%
>95%
~90%
1,8-Diazabicyclo[5.4.0]undec-7-ene (1.1equiv),
N- Methylpyrrolidone
1,8-Diazabicyclo[5.4.0]undec-7-ene (1.1 equiv),
N-methylpiperidine
1,8-Diazabicyclo[5.4.0]undec-7-ene (2 equiv), N-
Methylpiperidine
As shown in the Table 1, the optimized condition for
the formation of 3a was achieved by using 1.1 equiv of
1,8-diazabicyclo[5.4.0]undec-7-ene and N-methyl-piper-
idine as solvent. No further improvement was observed by
Scheme 2
R
S
R
O
-EtOH
S
R
S
O
OH
N
H
N
H
OEt
NH2
OEt
5
6
3
Br
R
O
SH
NH2
EtO
H
N
Br
O
R
NH2
R
S
O
S
4

Nov-Dec 2006
Regioselective One Pot Synthesis of 2-Alkyl/Aryl-4H-benzo[1,4]thiazine-3-one
via Microwave Irradiation
1643
Table 2
Entry
1.
1
2
3
Yield
(%)
2-Aminothio-phenol
R-CBr-CO2Et
Product
SH
Br
Me
S
Me
O
98
NH2
EtO
O
N
H
2a
3a
Me
O
Cl
S
Me
Cl
SH
2.
3.
Br
96
98
EtO
NH2
N
H
O
2a
3b
SH
Me
Me
Br
Me
O
S
Me
O
NH2
EtO
N
H
2b
3c
Cl
SH
Me
Me
4.
91
Br
Me
O
Cl
S
Me
O
NH2
EtO
N
H
2b
3d
SH
Br
CH2CH3
S
CH2CH3
O
5.
6.
7.
95
97
98
NH2
EtO
O
N
H
2c
3e
Cl
SH
Br
EtO
Br
CH2CH3
Cl
S
CH2CH3
NH2
N
H
O
O
2c
3f
SH
CH3
S
CH3
NH2
EtO
O
N
H
O
2d
3g
Cl
SH
Br
Cl
S
CH3
8.
9.
96
96
CH3
NH2
N
H
O
EtO
O
2d
3h
3i
SH
Br
S
CH3
CH3
NH2
EtO
O
N
H
O
2e
Cl
SH
Br
S
Cl
10.
91
CH3
CH3
NH2
EtO
O
N
H
O
2e
3j

1644
S. Kamila, B. Koh, O. Khan, H.M. Zhang, E.R. Biehl
Vol 43
Table 2
1
2
3
Yield
(%)
Entry
2-Aminothio-phenol
R-CBr-CO2Et
Product
SH
11.
68
Br
S
NH2
O
N
H
O
EtO
2f
3k
Cl
SH
12.
72
Br
Cl
S
NH2
O
N
H
O
EtO
2f
3l
General Procedure for the Preparation of 2-Alkyl/Aryl-4H-
benzo[1,4]thiazine-3-one.
Conclusion.
In summary, we have developed a regioselective, one
pot synthesis of 2-alkyl-4H-benzo[1,4]thiazine-3-ones
from commercially available ethyl-2-bromo-2-alkyl/aryl
acetate and 2-aminothiophenol under controlled micro-
wave heating without any solid support. The proper
combination of the base (1,8-diazabicyclo[5.4.0]undec-7-
ene and solvent (N-methylpiperidine) is critical for
achieving the regioselective products.
Compound 2a (~ 200 mg, 1 equivalent) was mixed with 2-
aminothiophenol (1.1 equivalent) and 1,8-diazabicyclo[5.4.0]-
undec-7-ene (1.2 equivalent) in a microwavable test tube. N-
Methylpiperidine (2 mL) was added to the tube which was then
capped and the mixture was irradiated with 150 psi pressure and at
a temperature of 180 °C for 4 minutes. After cooling, the reaction
mixture was dissolved in ethyl acetate (30 mL) and was washed
with brine. The ethyl acetate layer was separated and was dried
over sodium sulphate and evaporated under reduced pressure. The
crude reaction mixture was purified by column chromatography
using ethyl acetate-hexane (9:1, v/v) as eluent. The other
compounds prepared by this procedure are listed below.
2-Methyl-4H-benzo[1,4]thiazin-3-one (3a).
This compound was obtained as white solid. mp 124-126 °C
(ethyl acetate-hexane); 1H NMR (deuteriochloroform): ꢀ 1.53 (d,
J = 6.5 Hz, 3H, -CH3), 3.56-3.59 (m, 1H, -CH-), 6.98-7.03 (m,
2H, aromatic), 7.18-7.31 (m, 2H, aromatic), 9.90 (br s, 1H,
-NH); 13C NMR (deuteriochloroform): ꢀ 16.0 (CH3), 37.3 (CH),
117.6 (CH), 119.5 (C), 126.2 (CH), 127.5 (CH), 128.4 (CH),
136.5 (C), 169.9 (C).
Anal. Calcd. for C9H9NOS: C, 60.31; H, 5.06; N, 7.81. Found
C, 60.33; H, 5.08; N, 7.80.
ORTEP structure of 3a
7-Chloro-2-methyl-4H-benzo[1,4]thiazin-3-one (3b).
This compound was obtained as crystalline white solid, mp
184-186 °C (ethyl acetate-hexane); 1H NMR (acetone-d6) ꢀ: 1.42
(d, J = 6.4 Hz, 3H, CH3), 3.61-3.62 (m, 1H, CH), 7.04 (dd, J =
2.1 Hz, 7.8 Hz, 2H, aromatic), 7.33 (s, 1H, aromatic), 9.66 (br s,
1H, -NH); 13C NMR (acetone-d6): ꢀ 15.0 (CH3), 36.5 (CH),
116.8 (CH), 118.4 (C), 123.1 (CH), 129.3 (CH), 132.3 (C),
138.8 (C), 167.7 (C).
EXPERIMENTAL
Melting points and boiling points were taken on a Mel-Temp
capillary apparatus and are uncorrected with respect to stem
correction. 1H and 13C NMR spectra were recorded on a 400 MHz
Bruker ADVANCE DRX-400 Multinuclear NMR spectrometer.
Chemical shifts are reported in reference to TMS as internal
standard. Microwave experiments were carried out in CEM-Driver
microwave. Elemental analyses were obtained from Southern
Methodist University Analytical Service Laboratories. All
chemicals were purchased from Fisher Scientific or Aldrich
chemicals and were used without any further purification.
Anal. Calcd. for C9H8ClNOS: C, 59.59; H, 3.77; N, 6.55.
Found C, 59.61; H, 3.81; N, 6.56.
2,2-Dimethyl-4H-benzo[1,4]thiazin-3-one (3c).
This compound was obtained as colorless solid, mp 108-109
°C (ethyl acetate-hexane); 1H NMR (deuteriochloroform): ꢀ 1.52

Nov-Dec 2006
Regioselective One Pot Synthesis of 2-Alkyl/Aryl-4H-benzo[1,4]thiazine-3-one
via Microwave Irradiation
1645
(d, 6H, -CH3 X2), 6.98 (d, J = 7.8 Hz, 1H, aromatic), 7.03 (d, J =
7.8 Hz, 1H, aromatic), 7.19 (dd, J = 7.5, 7.8 Hz, 1H, aromatic),
7.29 (d, J = 7.5 Hz, 1H, aromatic), 9.71 (br s, 1H, -NH); 13C
NMR (deuteriochloroform): ꢀ 24.7 (CH3 X2), 42.8 (C), 117.0
(CH), 120.1 (C), 123.9 (CH), 127.3 (CH), 128.2 (CH), 136.6
(C), 171.9 (C).
-CH), 6.97-7.00 (m, 2H, aromatic), 7.23 (d, J = 7.8 Hz, 1H,
aromatic), 10.23 (br s, 1H, -NH); 13C NMR (deuteriochloro-
form): ꢀ 13.8 (CH3), 20.2 (CH2), 32.1 (CH2), 46.6 (-CH), 117.4
(CH), 124.2 (CH), 129.5 (CH), 132.9 (C), 137.6 (C), 169.5 (C).
Anal. Calcd. for C11H12 ClNOS: C, 54.65; H, 5.00; N, 5.79.
Found C, 54.67; H, 5.08; N, 5.80.
Anal. Calcd. for C10H11NOS: C, 62.15; H, 5.74; N, 7.25.
Found C, 62.23; H, 5.74; N, 7.28.
2-Butyl-4H-benzo[1,4]thiazin-3-one (3i).
This compound was obtained as pinkish white solid, mp 94-
1
96 °C (ethyl acetate-hexane); H NMR (deuterio-chloroform): ꢀ
7-Chloro-2,2-dimethyl-4H-benzo[1,4]thiazin-3-one (3d).
This compound was obtained as a crystalline colorless solid,
mp 79-80 °C (ethyl acetate-hexane); H NMR (deuterio-chloro-
0.90 (t, 3H, CH3), 1.32-1.43 (m, 3H, -CH2), 1.57-1.64 (m, 2H, -
CH2), 1.89-1.98 (m, 1H, -CH2), 3.39-3.43 (m, 1H, -CH), 6.97 (d,
J = 7.8 Hz, 1H, aromatic), 7.01 (dd, J =7.5, 7.8 Hz, 1H,
aromatic), 7.18 (dd, J= 7.8, 8.1 Hz, 1H, aromatic), 7.31 (d, J =
7.8 Hz, 1H, aromatic), 9.89 (br s, 1H, NH); 13C NMR (deuterio-
chloroform) ꢀ: 14.2 (CH3), 22.5 (CH2), 29.2 (CH2), 29.9 (CH2),
43.0 (CH), 117.5 (CH), 118.9 (C), 124.2 (CH), 127.4(CH),
128.6 (CH), 136.4 (C), 169.4 (C).
1
form): ꢀ 1.51 (s, 6H, CH3 X2), 6.94 (d, J = 2.1 Hz, 1H,
aromatic), 7.01 (dd, J = 2.1 Hz, 7.8 Hz, 1H, aromatic), 7.23 (d, J
= 7.8 Hz, 1H, aromatic), 9.09 (br s, 1H, -NH); 13C NMR
(deuteriochloroform): ꢀ 24.6 (CH3 X2), 42.8 (C), 116.8 (CH),
118.7 (C), 124.0 (CH), 129.3 (CH), 132.9 (C), 137.4 (C), 171.4
(C).
Anal. Calcd. for C10H10ClNOS: C, 52.75; H, 4.43; N, 6.15.
Found: C, 52.76; H, 4.45; N, 6.15.
Anal. Calcd. for C12H15NOS: C, 65.12; H, 6.83; N, 6.33.
Found: C, 65.15; H, 6.88; N, 6.39.
2-Ethyl-4H-benzo[1,4]thiazin-3-one (3e).
2-Butyl-7-chloro-4H-benzo[1,4]thiazin-3-one (3j).
This compound was obtained as colorless solid, mp 102-104
°C (ethyl acetate-hexane); 1H NMR (deuteriochloroform): ꢀ 1.09
(t, 3H, -CH3), 1.62-2.00 (m, 2H, -CH2-), 3.49 (t, 1H, -CH-), 6.97
(d, J = 7.7 Hz, 1H, aromatic), 7.01 (dd, J = 7.5 Hz, 7.7 Hz, 2H,
aromatic), 7.18 (dd, J = 7.5, 7.8 Hz, 1H, aromatic), 7.31 (d, J =
7.8 Hz, 1H, aromatic), 9.91 (br s, 1H, -NH); 13C NMR
(deuteriochloroform): ꢀ 11.8 (CH3), 23.7 (CH2), 44.7 (CH),
117.4 (CH), 118.8 (C), 124.2 (CH), 127.4 (CH), 128.6 (CH),
136.4 (C), 169.3 (C).
This compound was obtained as white powdered solid, mp
109-111 °C (ethyl acetate-hexane); 1H NMR (deuterio-
chloroform): ꢀ 0.90 (t, 3H, CH3), 1.34-1.41 (m, 3H, -CH2), 1.55-
1.61 (m, 2H, -CH2), 1.91-1.95 (m, 1H, -CH2), 3.38-3.42 (m, 1H,
-CH), 6.99 (dd, J =2.5, 7.8 Hz, 2H, aromatic), 7.23 (d, J =7.8
Hz, 1H, aromatic), 10.00 (br s, 1H, NH); 13C NMR (deuterio-
chloroform): ꢀ 14.2 (CH3), 22.5 (CH2), 29.1 (CH2), 29.8 (CH2),
42.8 (CH), 117.4 (CH), 124.2 (CH), 129.5 (CH), 132.9 (C),
137.4 (C), 169.3 (C).
Anal. Calcd. for C10H11NOS: C,62.15; H, 5.74; N, 7.25.
Found: C, 62.18; H, 5.79; N, 7.26.
Anal. Calcd. for C12H14ClNOS: C, 60.31; H, 5.06; N, 7.81.
Found: C,56.35; H, 5.52; N, 5.48.
7-Chloro-2-ethyl-4H-benzo[1,4]thiazin-3-one (3f).
2-Phenyl-4H-benzo[1,4]thiazin-3-one (3k).
This compound was obtained as a white fluffy solid, mp 151-
153 °C (ethyl acetate-hexane); 1H NMR (deuterio-chloroform): ꢀ
1.08 (t, 3H, -CH3), 1.63-1.98 (m, 2H, -CH2-), 3.33 (t, 1H, -CH-),
6.97-7.00 (m, 2H, aromatic), 7.22-7.27 (m, 1H, aromatic), 9.98
(br s, 1H, -NH); 13C NMR (deuteriochloroform): ꢀ 11.7 (CH3),
23.6 (CH2), 44.6 (CH), 117.3 (CH), 124.3 (CH), 129.5 (CH),
132.9 (C), 137.4 (C), 169.2 (C).
This compound was obtained as yellowish solid, mp 181-183
°C (ethyl acetate-hexane); 1H NMR (deuteriochloroform): ꢀ 4.71
(s, 1H, CH), 6.88 (d, J = 7.8 Hz, 1H, aromatic), 7.02 (dd, J =7.5,
7.8 Hz, 1H, aromatic), 7.17 (dd, J =7.8, 7.8 Hz, 1H, aromatic),
7.29-7.4 (m, 6H, aromatic), 9.04 (br s, 1H, NH); 13C NMR
(deuteriochloroform): ꢀ 46.6 (CH), 120.1 (CH), 124.4 (CH),
127.6 (C), 128.3 (CH), 128.6 (CH), 129.1 (CH), 135.3 (C),
138.9 (C), 167.3 (C).
Anal. Calcd. for C10H10ClNOS: C, 52.75; H, 4.43; N, 6.15.
Found: C, 52.80; H, 4.48; N, 6.15.
Anal. Calcd. for C14H11CNOS: C, 69.68; H, 4.59; N, 5.80.
Found C, 69.71; H, 4.63; N, 5.83.
2-Propyl-4H-benzo[1,4]thiazin-3-one (3g).
7-Chloro-2-phenyl-4H-benzo[1,4]thiazin-3-one (3l).
This compound was obtained as pink solid, mp 66-68 °C
(ethyl acetate-hexane); 1H NMR (deuteriochloroform): ꢀ 0.93 (t,
3H, -CH3), 1.45-1.89 (m, 4H, -CH2- X2), 3.42-3.45 (m, 1H, -
CH), 7.00 (dd, J = 7.2 Hz, 7.8 Hz, 2H, aromatic), 7.17 (dd, J =
7.5, 7.8 Hz, 1H, aromatic), 7.30 (d, J =7.5 Hz, 1H, aromatic),
10.31 (br s, 1H, -NH); 13C NMR (deuteriochloroform): ꢀ 13.9
(CH3), 20.3 (CH2), 32.3 (CH2), 42.7 (CH), 117.5 (CH), 118.8
(C), 124.2 (CH), 127.4 (CH), 128.5 (CH), 136.5 (C), 169.6 (C).
Anal. Calcd. for C11H13NOS: C, 63.74; H, 6.32; N, 6.76.
Found: C, 63.78; H, 6.39; N, 6.78.
This compound was obtained as brownish solid, mp 176-178 °C
(ethyl acetate-hexane); 1H NMR (deuteriochloroform): ꢀ 4.76 (s, 1H,
CH), 6.83 (d, J =7.8 Hz, 1H, aromatic), 7.03 (dd, J = 7.5, 7.8 Hz, 1H,
aromatic), 7.18 (dd, J =1.5, 7.8 Hz, 1H, aromatic), 7.31-7.45 (m, 5H,
aromatic), 9.21 (br s, 1H, NH); 13C NMR (deuteriochloroform): ꢀ
46.7 (CH), 120.8 (CH), 127.5 (CH), 128.5 (CH), 128.9 (C), 129.1
(CH), 129.6 (C), 135.8 (C), 137.0 (C), 168.0 (C).
Anal. Calcd. for C14H10ClNOS: C, 60.98; H, 3.66; N, 5.08.
Found C, 61.01; H, 3.69; N, 5.09.
7-Chloro-2-propyl-4H-benzo[1,4]thiazin-3-one (3h).
X-ray Analysis of Compound 3a.
This compound was obtained as white solid, mp 125-127 °C
(ethyl acetate-hexane); 1H NMR (deuteriochloroform): ꢀ 0.94 (t,
3H, -CH3), 1.44-1.89 (m, 4H, -CH2- X2), 3.41-3.45 (m, 1H,
Crystal data are as follows: C9H9NOS, formula weight 179.23,
triclinic, space group P-1, a = 4.6992(6), b = 8.6605(11), c =
11.5069(15) Å, ꢀ = 112.040(2)°, ꢁ = 91.683(2)°, ꢂ = 93.911(2)°,

1646
S. Kamila, B. Koh, O. Khan, H.M. Zhang, E.R. Biehl
Vol 43
v = 432.30(10) Å3, z = 2, d = 1.377 g/cm, μ = 0.321 mm-1. Data
Potent Aldose Reductase Inhibitors: 4-Benzyl-and 4-(Benzothiazol-2-yl
methyl)-3,4-dihydro-3-oxo-2H-1,4-benzothiazine-2-acetic Acid
Derivatives. Chem. Pharm. Bull., 42, 1264-1271 (1994).
[2] R. R. Gupta, P. K. Dev, M. L. Sharma, C. M. Rajoria, A.
Gupta, M. Nyati, Anticancer Activities of 2,3-dihydro-1,4-
benzothiazines, and of their 4-(N-alkyl amides) and 4-(N-alkyl N-
nitrosoamides), Anti-Cancer Drugs, 4, 589-592 (1993).
[3a] A. S. Angeloni, G. Pappalardo, Gazz. Chim. Ital., 91, 633,
(1961); Chem. Abstr., 56, 10136e (1962); [b] N. Jacob-Sen, H. Lolind-
Andersen, Synthesis, 911 (1990); [c] M. Hori, T. Kataoka, H. Shimizu,
Y. Imai, Chem. Pharm. Bull., 27, 1973 (1979).
were collected on
a Bruker-AXS P4 diffractometer,
MoKꢀ, 2ꢁ 1.91-28.34. Data were corrected for Lorentz and
polarization effects, as well as for absorption. The structure was
solved by direct methods and refined with SHELX97 [6]. There
are two independent molecules in an asymmetric unit. H atoms
are located in calculated positions. The final refinement
converge at R1= 0.049. wR2 (all data) 0.128.
Acknowledgement.
[4a] R. N. Prasad, K. Tietie, Can. J. Chem., 44, 1247 (1966); [b]
R. T. Coutts, D. L. Barton, E. M. Smith, Can. J. Chem., 44, 1733,
(1966); [c] J. M. Teulon, EP, 162, 176 (1985); Chem. Abstr., 104,
109668r (1986)]
We thank the Welch Foundation, Houston, TX for partial
financial support for this work.
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