Microwave-assisted one-pot synthesis of benzo[b][1,4]thiazin-3(4H)-ones via Smiles rearrangement

Article abstract of DOI:10.1016/j.tet.2008.07.059

The synthesis of benzo[b][1,4]thiazin-3(4H)-one derivatives in a simple and efficient method from the one-pot reaction of substituted 2-chlorobenzenthiols, chloroacetyl chloride, and primary amines via Smiles rearrangement under microwave irradiation gave high yields (65-92%) of the products with short reaction time (15-20 min).

Full text of DOI:10.1016/j.tet.2008.07.059

Tetrahedron 64 (2008) 9669–9674
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Microwave-assisted one-pot synthesis of benzo[b][1,4]thiazin-3(4H)-ones via
Smiles rearrangement
,
,
*
Hua Zuo a c, Zhu-Bo Li a, Fang-Kui Ren a, J.R. Falck b, Meng Lijuan c, Chuljin Ahn c, Dong-Soo Shin c
a College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China
b Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
c Department of Chemistry, Changwon National University, Changwon, GN 641-733, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 June 2008
Received in revised form 17 July 2008
Accepted 17 July 2008
Available online 22 July 2008
The synthesis of benzo[b][1,4]thiazin-3(4H)-one derivatives in a simple and efficient method from the
one-pot reaction of substituted 2-chlorobenzenthiols, chloroacetyl chloride, and primary amines via
Smiles rearrangement under microwave irradiation gave high yields (65–92%) of the products with short
reaction time (15–20 min).
Ó 2008 Published by Elsevier Ltd.
Keywords:
Benzo[b][1,4]thiazin-3(4H)-one
Microwave
Smiles rearrangement
2-Chlorobenzenethiol
One-pot
1. Introduction
ongoing studies on the development of new routes for the prepa-
ration of biologically active heterocyclic compounds,17 we herein
For heterocycles containing sulfur moieties, benzo[b][1,4]thia-
zin-3(4H)-one derivatives’ scaffold are classified as privileged
structures due to the large number of biologically active molecules
and natural products containing this moiety.1–13
used substituted 2-chlorobenzenethiol 1, chloroacetyl chloride, and
primary amine 2 under microwave (MW) irradiation to synthesize
benzo[b][1,4]thiazin-3(4H)-ones via Smiles rearrangement as one-
pot reaction (Scheme 1). This method afforded an easy and efficient
way to prepare benzo[b][1,4]thiazin-3(4H)-ones and permitted
us to introduce great molecular diversity, including substitution
diversity and skeleton diversity of benzo[1,4]thiazin-3(4H)-ones.
To date, the benzo[b][1,4]thiazin-3(4H)-one scaffold has been
generated by several methods involving: (i) direct cyclization from
2-aminobenzenethiol by reacting with halo acetyl halide;14 (ii)
starting from halonitrophenol followed by substitution of halo
atom by thiol acetates and then reduction to form ring system;10,15
(iii) treatment of 2-chloroaniline with sodium sulfide, followed
by the reaction with chloroacetic acid for cyclization.7,8 However,
the limited kinds of 2-aminobenzenethiol, halonitrophenol, and
2-chloroaniline hindered the structural diversity of benzo[1,4]-
thiazin-3(4H)-ones. Other challenges in this field are low yield
because of multi-step and expensive catalysts used in the reported
methods.
R
SH
Cl
N
O
Cs2CO3, DMF
Cl
+
Cl
+
RNH2
i) 0 °C, ii) 150 °C, MW
O
S
Cl
Cl
1
2
3
R = alkyl, aryl
Scheme 1. One-pot synthesis of benzo[1,4]thiazin-3(4H)-ones.
Recently, we reported the one-pot synthesis of benzo[b]-
[1,4]oxazin-3(4H)-ones under microwave irradiation via Smiles
rearrangement.16 We have found that the good results were
obtained using substituted 2-chlorophenols (1.0 equiv) and pri-
mary amines (1.2 equiv) in the presence of Cs2CO3 (3.6 equiv). In an
2. Results and discussions
Substituted 2-chlorobenzenethiol 1, chloroacetyl chloride, and
primary amine 2 in the presence of Cs2CO3 in dry DMF underwent
a fast 1:1:1 addition reaction at 150 ꢀC under microwave for less
than 20 min to produce corresponding benzo[b][1,4]-thiazin-
3(4H)-ones. The results were excellent in terms of yields (65–92%),
* Corresponding author. Tel.: þ82552133437; fax: þ82552133439.
E-mail address: dsshin@changwon.ac.kr (D.-S. Shin).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.07.059

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H. Zuo et al. / Tetrahedron 64 (2008) 9669–9674
Table 1
Microwave-assisted one-pot synthesis of benzo[b][1,4]thiazin-3(4H)-onesa
Entry
Benzenethiol
Amine
Productb
Time (min)
18
Yieldc (%)
Bn
N
SH
NH2
O
1
3a
3b
85
Cl
S
Cl
1a
2a
Cl
N
O
NH2
2
1a
15
82
2b
S
Cl
NH2
N
S
O
3
4
1a
1a
3c
20
20
65
86
2c
Cl
O
O
3d
N
S
O
2d
NH2
NH2
Cl
Bn
N
SH
O
5
6
3e
3f
18
18
92
90
Cl
Cl
2a
Cl
S
1b
NH2
N
S
O
1b
2b
Cl
NH2
7
8
1b
3g
3h
18
20
80
84
N
S
O
2c
Cl
O
O
1b
N
O
2d
NH2
NH2
Cl
Cl
S
Bn
N
Cl
SH
Cl
O
9
3i
3j
18
18
85
72
2a
1c
S
NH2
Cl
N
S
O
10
1c
1c
2b
NH2
11
12
3k
20
18
80
75
Cl
N
S
O
2c
O
O
1c
3l
Cl
N
O
2d
NH2
S

H. Zuo et al. / Tetrahedron 64 (2008) 9669–9674
9671
Table 1 (continued )
Entry
Benzenethiol
Amine
Productb
Time (min)
18
Yieldc (%)
Cl
Cl
Bn
N
NH2
SH
O
13
14
3m
3n
85
72
Cl
S
2a
1d
Cl
NH2
N
S
O
1d
1d
18
20
2b
NH2
Cl
15
3o
3p
80
73
N
S
O
2c
O
O
Cl
16
1d
18
N
O
2d
NH2
S
a
Reaction conditions: ClCH2COCl, Cs2CO3, (i) 0 ꢀC (ii) 150 ꢀC, MW.
All the products were characterized by mp, MS, 1H, and 13C NMR spectra.
Isolated yields after column purification.
b
c
reaction time (15–20 min), and product purity. The nature of these
compounds as 1:1:1 adducts was apparent from their mass spectra,
which displayed, in each case, the molecular ion peak at appro-
priate m/z values. IR, 1H, and 13C NMR, GC–MS spectral data fully
supported the predicted structures.
efficient route for preparing a variety of benzo[1,4]thiazin-3(4H)-
ones. Representative primary amines possessing a straight-chain
alkyl group, branched-chain alkyl group, aryl group, and tetrahy-
drofuran group reacting with substituted chlorobenzenethiols
afforded 3 in high yields (entries 1–16).
In view of the high efficiency of Cs2CO3/DMF system in our
earlier work on the synthesis of the benzo[b][1,4]oxazin-3(4H)-
ones,16 we chose it as a base to perform this one-pot reaction of
benzo[1,4]thiazin-3(4H)-ones, and the results were given in Table 1.
The desired benzo[1,4]thiazin-3(4H)-one 3a was obtained by the
reaction of 2,3-dichlorobenzenethiol 1a and benzyl amine 2a in the
presence of Cs2CO3 at 150 ꢀC for 18 min in 85% yield (entry 1).
Accordingly, the other benzo[1,4]thiazin-3(4H)-ones were also
performed in the same approach yielding from 65% to 92% (entries
2–16). It is interesting to note that the position of chloro at aromatic
ring did not interfere with the outcome of the reaction. The pres-
ence of an alkyl or aryl substituent of amine also did not show any
significant influence on the reaction. In all cases studied, Cs2CO3/
DMF exhibited a good system, while either decreasing the ratio of
Cs2CO3 or using K2CO3 instead of Cs2CO3 only caused the incom-
pletion of the reaction. This method provided a convenient and
The formation of 3a was confirmed by the reaction of 2-amino-
6-benzenethiol 4 with chloroacetyl chloride using known method
(Scheme 2). Chloroacetyl chloride was reacted with 4 to afford the
intermediate 5, which was cyclized to afford 6. Compound 6 was
then treated with benzyl chloride to furnish compound 3a.
Product 3a obtained by two different synthetic routes, that is,
from 1a (Scheme 1) and from 4 (Scheme 2) was compared using
physical and spectral data. Rf value of TLC, melting point, GC–MS,
and NMR spectral data of the two compounds were found to be
the same.
The formation of benzo[b][1,4]thiazin-3(4H)-ones is explained
by a mechanism in Scheme 3 (exemplified by 3a). As the reaction is
conducted in the presence of Cs2CO3 as base, it facilitates the for-
mation of S-alkylated product.
It is then possible for the cyclization by Smiles rearrangement
via two steps: the spiro-type intermediate was formed in the first
H
H
N
NH2
SH
N
O
K2CO3
Cl
ClCH2COCl, K2CO3
O
CH3CN, reflux
1 h, 82%
CH3CN, rt
2 h, 92%
S
SH
Cl
Cl
4
Cl
5
6
BnCl, K2CO3
DMF, reflux
1 h, 78%
Bn
N
O
S
Cl
3a
Scheme 2. Alternative route for the synthesis of 3a.

9672
H. Zuo et al. / Tetrahedron 64 (2008) 9669–9674
Cl
4.2.1. 4-Benzyl-8-chloro-2H-benzo[b][1,4]thiazin-3(4H)-one (3a)
A light-yellow powder; mp 96–97 ꢀC; IR (KBr) /cmꢁ1: 3070,
3026, 3001, 2955, 2916, 1662, 1575, 1562, 1494, 1450, 1375, 1312,
1275, 1148, 883, 776, 733, 698; 1H NMR (400 MHz, CDCl3)
: 3.53 (s,
2H), 5.20 (s, 2H), 6.92 (dd, J¼8.0,1.2 Hz,1H), 7.00–7.09 (m, 2H), 7.17–
7.33 (m, 5H); 13C NMR (100 MHz, CDCl3)
: 31.1, 48.8, 116.6, 124.6,
Cl
n
Bn
NH
O
Cl
Cl
HS
Cl
O
O
NHBn
Cl
d
1a
Cl
BnNH2
Cs2CO3
S
d
2a
126.3,127.1,127.4,128.9,129.1,132.6,136.3,140.8,164.9; MS (EI) m/z:
289 (Mþ, 69%), 246 (7), 170 (28), 134 (7), 108 (7), 91 (100), 65 (12).
Cl
Cl
Cl
Cl
H
H
S
S
S
Cs2CO3
-Cl
4.2.2. 8-Chloro-4-hexyl-2H-benzo[b][1,4]thiazin-3(4H)-one (3b)
- HCl
O
N
Bn
A light-yellow oil; IR (KBr)
1675, 1578, 1564, 1452, 1377, 1306, 1269, 1144, 1056, 772, 740, 708;
1H NMR (400 MHz, CDCl3)
n
/cmꢁ1: 3068, 2955, 2929, 2858,
O
N
Bn
N
Bn
O
3a
d
: 0.87 (t, J¼6.4 Hz, 3H), 1.30–1.36 (m,
6H), 1.56–1.65 (m, 2H), 3.38 (s, 2H), 3.97 (t, J¼7.6 Hz, 2H), 7.04 (d,
Scheme 3. Proposed mechanism.
J¼8.0 Hz, 1H), 7.12 (d, J¼8.0 Hz, 1H), 7.18 (t, J¼8.0 Hz, 1H); 13C NMR
step, and was rearranged in the second step with the loss of HCl
yielding compound 3a.
(100 MHz, CDCl3) d: 14.0, 22.6, 26.4, 27.4, 31.2, 31.4, 45.2, 116.1,
124.3, 124.8, 127.0, 132.8, 140.5, 164.5; MS (EI) m/z: 283 (Mþ, 55%),
236 (69), 212 (23), 199 (100), 184 (55), 170 (48), 154 (11), 134 (12),
108 (10).
3. Conclusions
4.2.3. 8-Chloro-4-cyclohexyl-2H-benzo[b][1,4]thiazin-
A new and one-pot route to benzo[b][1,4]thiazin-3(4H)-ones by
microwave irradiation via Smiles rearrangement was developed.
The use of simple starting materials, moderate to excellent yields,
short reaction time, and easy purification procedure present the
notable advantages of this method. The chemistry developed
herein together with our previous work should be thus particularly
useful in the diversity-oriented synthesis of oxazin-3(4H)-ones and
thiazin-3(4H)-ones. To the best of our knowledge, this new pro-
cedure provides the first example of the efficient synthetic method
for benzo[b][1,4]thiazin-3(4H)-ones by a one-pot reaction via
Smiles rearrangement. Studies on the biological activities of these
products are currently undergoing.
3(4H)-one (3c)
An off-white solid; mp 110–112 ꢀC; IR (KBr) /cmꢁ1: 3008, 2955,
n
2925, 2853, 1670, 1575, 1561, 1448, 1342, 1313, 1131, 1078, 773, 740,
712, 687; 1H NMR (400 MHz, CDCl3)
: 1.21–1.41 (m, 3H), 1.78–1.87
(m, 4H), 2.23–2.33 (m, 2H), 3.29 (s, 2H), 4.05–4.13 (m, 1H), 7.11–7.18
d
(m, 3H); 13C NMR (100 MHz, CDCl3)
d: 25.4, 26.5, 30.2, 33.5, 61.4,
117.9, 124.7, 126.6, 127.3, 132.9, 141.7, 166.6; MS (EI) m/z: 281 (Mþ,
33%), 199 (100), 170 (42), 154 (15), 55 (8).
4.2.4. 8-Chloro-4-((tetrahydrofuran-2-yl)methyl)-2H-
benzo[b][1,4]thiazin-3(4H)-one (3d)
A light-yellow oil; IR (KBr)
1578, 1563, 1454, 1433, 1376, 1305, 1271, 1149, 1075, 1053, 942, 774,
741, 709; 1H NMR (400 MHz, CDCl3)
: 1.48–1.56 (m, 1H), 1.77–1.91
n
/cmꢁ1: 3081, 2973, 2952, 2871, 1674,
4. Experimental section
4.1. General
d
(m, 2H), 1.93–2.02 (m, 1H), 3.32 (dd, J¼20.8, 14.4 Hz, 2H), 3.63–3.70
(m, 2H), 3.82 (dd, J¼15.2, 7.2 Hz, 1H), 4.08–4.14 (m, 1H), 4.24 (dd,
J¼14.4, 3.6 Hz, 1H), 7.03 (dd, J¼8.0, 1.2 Hz, 1H), 7.09 (t, J¼8.0 Hz, 1H),
1H and 13C NMR spectra were recorded in CDCl3 (400 MHz for 1H
and 100 MHz for 13C, respectively) with TMS as the internal refer-
ence on Bruker Advance 400 FT spectrometer. Chemicals shifts
were reported in parts per million. Mass spectra (MS) were mea-
sured by the EI method. Melting points are uncorrected. Silica gel
(70–230 mesh) was used for flash column chromatography. All the
reactions were monitored by TLC using 0.25 mm silica gel plates
(Merck 60F254) with UV indicator. All microwave-assisted reactions
were carried out on KMIC-1.5 kW creator from Korea Microwave
Instrument Company. The microwave-assisted reaction time is the
hold time at the final temperature. All chemicals were used as
delivered from Sigma–Aldrich or Acros. N,N-Dimethyl-formamide
was distilled from anhydrous magnesium sulfate prior to use.
Acetonitrile was distilled over phosphorus oxide before use.
7.39 (dd, J¼8.0, 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d: 25.6, 29.5,
31.3, 50.4, 68.2, 77.0, 117.7, 124.5, 124.8, 127.1, 132.3, 141.4, 164.8; MS
(EI) m/z: 283 (Mþ, 10%), 213 (18), 199 (75), 184 (19), 170 (19), 108
(11), 85 (35), 71 (100), 43 (26).
4.2.5. 4-Benzyl-7-chloro-2H-benzo[b][1,4]thiazin-3(4H)-one (3e)
A colorless oil; IR (KBr)
n
/cmꢁ1: 3063, 3027, 2928, 1665, 1584,
1477, 1405, 1360, 1317, 1266, 1234, 1141, 1106, 875, 812, 723, 693; 1H
NMR (400 MHz, CDCl3)
d
: 3.50 (s, 2H), 5.20 (s, 2H), 6.90 (d, J¼8.8 Hz,
1H), 7.03 (dd, J¼8.8, 2.4 Hz, 1H), 7.16–7.33 (m, 6H); 13C NMR
(100 MHz, CDCl3) d: 31.4, 48.4, 119.3, 125.6, 126.3, 127.6, 127.4, 128.0,
128.8, 128.9, 136.2, 138.2, 165.0; MS (EI) m/z: 289 (Mþ, 55%), 170
(15), 91 (100), 65 (10).
4.2.6. 7-Chloro-4-hexyl-2H-benzo[b][1,4]thiazin-3(4H)-one (3f)
4.2. General procedure for the synthesis of
benzo[b][1,4]thiazin-3(4H)-ones (3)
A colorless oil; IR (KBr)
1583,1563,1476,1403,1362,1311,1266,1138,1112, 869, 810, 782; 1H
NMR (400 MHz, CDCl3)
: 0.87 (t, J¼6.4 Hz, 3H), 1.24–1.34 (m, 6H),
n
/cmꢁ1: 3065, 2955, 2929, 2858, 1674,
d
To a magnetically stirred solution of the appropriate primary
amine 2 (1.0 mmol) and Cs2CO3 (3.6 mmol) in dry DMF cooled by
ice bath were added chloroacetyl chloride (1.1 mmol) and 1
(0.8 mmol). The reaction mixture was then placed into microwave
oven (KMIC-1.5 kW) at 150 ꢀC and irradiated for the period listed in
Table 1. The solvent was removed under vacuum and the residue
was poured into water. It was then extracted by ethyl acetate. The
combined organic layers were dried over anhydrous MgSO4 and
evaporated under vacuum to obtain the crude product. Pure
product was obtained by column chromatography on silica gel.
1.61 (t, J¼6.4 Hz, 2H), 3.37 (s, 2H), 3.96 (t, J¼7.6 Hz, 2H), 7.03 (d,
J¼8.8 Hz, 1H), 7.19 (dd, J¼8.8, 2.0 Hz, 1H), 7.34 (d, J¼2.0 Hz, 1H); 13
C
NMR (100 MHz, CDCl3) d: 14.0, 22.6, 26.3, 27.3, 31.4, 31.5, 44.8,118.8,
125.9,127.1,128.1,128.4,138.0,164.6; MS (EI) m/z: 283 (Mþ, 55%), 236
(45), 212 (21), 199 (100), 184 (49), 170 (42), 154 (10), 134 (9), 108 (9).
4.2.7. 7-Chloro-4-cyclohexyl-2H-benzo[b][1,4]thiazin-
3(4H)-one (3g)
A colorless oil; IR (KBr)
1560, 1474, 1453, 1416, 1382, 1347, 1315, 1289, 1261, 1237, 1142, 1109,
n
/cmꢁ1: 3065, 2931, 2854, 1671, 1581,

H. Zuo et al. / Tetrahedron 64 (2008) 9669–9674
9673
895, 868, 819, 788; 1H NMR (400 MHz, CDCl3)
d
: 1.21–1.41 (m, 3H),
(19), 199 (100), 184 (18), 170 (17), 134 (9), 108 (12), 85 (19), 71 (100),
43 (23).
1.68 (d, J¼12.4 Hz,1H),1.77–1.87 (m, 4H), 2.20–2.29 (m, 2H), 3.28 (s,
2H), 4.07–4.15 (m, 1H), 7.17–7.18 (m, 2H), 7.36 (t, J¼1.2 Hz, 1H);
13C NMR (100 MHz, CDCl3)
d
: 25.4, 26.5, 30.2, 33.7, 60.1, 120.7, 126.8,
4.2.13. 4-Benzyl-5-chloro-2H-benzo[b][1,4]thiazin-3(4H)-one (3m)
128.3, 128.4, 128.7, 139.0, 166.7; MS (EI) m/z: 281 (Mþ, 27%), 199
A light-yellow oil; IR (KBr) n
/cmꢁ1: 3064, 3030, 2961, 2927, 1682,
(100), 170 (33), 154 (11), 55 (8).
1573,1557,1496,1443,1355,1303,1261,1226,1206,1134,1110,1081,
1028, 903, 800, 774, 732, 722, 698, 675; 1H NMR (400 MHz, CDCl3)
d
: 3.27 (s, 2H), 5.31 (s, 2H), 6.82 (t, J¼7.6 Hz, 1H), 7.03–7.10 (m, 6H),
4.2.8. 7-Chloro-4-((tetrahydrofuran-2-yl)methyl)-2H-
7.16 (dd, J¼7.6, 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d: 34.2, 48.8,
benzo[b][1,4]thiazin-3(4H)-one (3h)
A light-yellow oil; IR (KBr)
1563, 1477, 1402, 1357, 1308, 1267, 1237, 1109, 1084, 868, 810, 782;
1H NMR (400 MHz, CDCl3)
: 1.55–1.64 (m, 1H), 1.86–1.99 (m, 2H),
n
/cmꢁ1: 3093, 2973, 2872, 1674, 1584,
125.4, 127.0, 127.2, 127.3, 127.7, 128.2, 129.6, 133.1, 136.5, 136.9,
167.5; MS (EI) m/z: 289 (Mþ, 40%), 246 (8),183 (10),170 (40),134 (8),
91 (100), 65 (11).
d
2.02–2.10 (m, 1H), 3.39 (dd, J¼31.6, 14.4 Hz, 2H), 3.68–3.78 (m, 2H),
3.46 (J¼15.2, 7.2 Hz, 1H), 4.16–4.23 (m, 1H), 4.33 (dd, J¼14.4, 4.0 Hz,
1H), 7.19 (dd, J¼8.8, 2.4 Hz, 1H), 7.33 (d, J¼2.4 Hz, 1H), 7.48 (d,
4.2.14. 5-Chloro-4-hexyl-2H-benzo[b][1,4]thiazin-3(4H)-one (3n)
A light-yellow oil; IR (KBr)
1573, 1557, 1444, 1358, 1303, 1261, 1219, 1207, 1133, 1102, 1083, 902,
800, 773, 724, 674; 1H NMR (400 MHz, CDCl3)
n
/cmꢁ1: 3064, 2956, 2928, 2857,1682,
J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
: 25.6, 29.5, 31.6, 50.1,
d
: 0.81 (t, J¼6.8 Hz,
68.2, 77.1, 120.5, 125.8, 127.2, 127.7, 128.7, 139.0, 164.9; MS (EI) m/z:
283 (Mþ, 14%), 213 (15), 199 (68), 184 (17), 170 (16), 151 (6), 108 (10),
85 (29), 71 (100), 43 (20).
3H), 1.17–1.25 (m, 6H), 1.42 (m, 2H), 3.32 (s, 2H), 4.12 (s, 2H), 7.02 (d,
J¼8.0 Hz, 1H), 7.28 (dd, J¼8.0, 0.8 Hz, 1H), 7.36 (dd, J¼8.0, 0.8 Hz,
1H); 13C NMR (100 MHz, CDCl3)
d: 14.0, 22.5, 26.2, 27.4, 31.3, 34.4,
46.4, 125.1, 127.1, 127.3, 130.0, 133.0, 137.3, 167.8; MS (EI) m/z: 283
(Mþ, 31%), 248 (20), 236 (27), 212 (15), 199 (100), 184 (44), 170 (53),
154 (13), 134 (15), 108 (7).
4.2.9. 4-Benzyl-6-chloro-2H-benzo[b][1,4]thiazin-3(4H)-one (3i)
A white solid; mp 105–106 ꢀC; IR (KBr) /cmꢁ1: 3080, 3054,
n
3032, 3000, 2974, 2923, 1658, 1576, 1559, 1494, 1474, 1456, 1416,
1368, 1349, 1313, 1253, 1229, 1139, 1103, 1081, 1030, 927, 893, 870,
4.2.15. 5-Chloro-4-cyclohexyl-2H-benzo[b][1,4]thiazin-
818, 779, 745, 717, 702, 674, 642; 1H NMR (400 MHz, CDCl3)
d: 3.51
3(4H)-one (3o)
(s, 2H), 5.20 (s, 2H), 6.95 (dd, J¼8.4, 2.0 Hz, 1H), 7.00 (d, J¼2.0 Hz,
A colorless oil; IR (KBr) n
/cmꢁ1: 3063, 2927, 2852, 1681, 1571,
1H), 7.20 (d, J¼8.4 Hz, 2H), 7.25–7.34 (m, 4H); 13C NMR (100 MHz,
1557, 1468, 1440, 1430, 1345, 1306, 1298, 1274, 1259, 1237, 1206,
CDCl3) d: 31.4, 48.5, 118.4, 122.2, 123.6, 126.3, 127.5, 129.0, 129.1,
1131, 1106, 1081, 1056, 895, 815, 792, 772, 725, 695; 1H NMR
132.9, 136.1, 140.6, 165.1; MS (EI) m/z: 289 (Mþ, 75%), 246 (7), 170
(400 MHz, CDCl3)
d
: 1.25–1.32 (m, 3H), 1.49 (d, J¼12.4 Hz, 1H), 1.48–
(25), 91 (100), 65 (12).
1.50 (m, 1H), 1.78–1.89 (m, 2H), 2.26–2.38 (m, 2H), 2.68–2.72 (m,
1H), 3.22 (s, 2H), 3.34–3.42 (m, 1H), 6.99 (t, J¼8.0 Hz, 1H), 7.29 (dd,
J¼8.0, 1.2 Hz, 1H), 7.34 (dd, J¼8.0, 1.2 Hz, 1H); 13C NMR (100 MHz,
4.2.10. 6-Chloro-4-hexyl-2H-benzo[b][1,4]thiazin-3(4H)-one (3j)
A light-yellow oil; IR (KBr)
1581, 1560, 1475, 1416, 1378, 1349, 1312, 1252, 1136, 1104, 964, 900,
857, 806, 726, 674; 1H NMR (400 MHz, CDCl3)
n
/cmꢁ1: 3051, 2955, 2929, 2857, 1678,
CDCl3) d: 25.5, 26.7, 30.8, 36.2, 66.4, 124.8, 126.9, 128.0, 129.6, 133.6,
140.1, 167.8; MS (EI) m/z: 281 (Mþ, 17%), 199 (100), 170 (57), 154
d
: 0.88 (t, J¼7.6 Hz,
(20), 134 (12), 55 (13), 41 (10).
3H), 1.25–1.38 (m, 6H), 1.59–1.66 (m, 2H), 3.36 (s, 2H), 3.95 (t,
J¼7.6 Hz, 2H), 6.99 (dd, J¼8.4, 2.0 Hz, 1H), 7.09 (d, J¼2.0 Hz, 1H),
4.2.16. 5-Chloro-4-((tetrahydrofuran-2-yl)methyl)-2H-
7.28 (d, J¼8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d: 14.0, 22.6, 26.3,
benzo[b][1,4]thiazin-3(4H)-one (3p)
27.3, 31.4, 31.5, 44.8, 118.0, 122.4, 123.2, 129.3, 132.8, 140.4, 164.7;
MS (EI) m/z: 283 (Mþ, 66%), 236 (63), 212 (22), 199 (100), 184 (44),
170 (41), 154 (17), 134 (11), 108 (11).
A white solid; mp 124–125 ꢀC; IR (KBr) /cmꢁ1: 3070, 3063,
n
2967, 2950, 2874, 1681, 1562, 1551, 1458, 1426, 1406, 1321, 1205,
1108, 1149, 1079, 1016, 919, 824, 775, 682; 1H NMR (400 MHz,
CDCl3) d: 1.48–1.55 (m, 1H), 1.84–1.98 (m, 3H), 3.14–3.21 (m, 1H),
3.47–3.53 (m, 1H), 3.68 (s, 2H), 3.68–3.77 (m, 1H), 3.84–3.89 (m,
4.2.11. 6-Chloro-4-cyclohexyl-2H-benzo[b][1,4]thiazin-
1H), 3.92–3.98 (m, 1H), 7.20–7.28 (m, 2H), 7.39 (d, J¼8.0 Hz,1H); 13
C
3(4H)-one (3k)
A colorless oil; IR (KBr) n
/cmꢁ1: 3067, 2931, 2854, 1675, 1580,
NMR (100 MHz, CDCl3) d: 25.8, 28.7, 38.7, 43.6, 68.1, 77.4, 129.0,
129.1, 130.4, 130.6, 131.6, 140.8, 167.8; MS (EI) m/z: 284 ([Mþ1]þ,
44%), 236 (10), 236 (27), 214 (13), 191 (16), 155 (6), 142 (27), 84 (59),
71 (100), 43 (29).
1558, 1472, 1453, 1422, 1384, 1343, 1312, 1247, 1236, 1135, 1101, 997,
977, 896, 862, 806, 791, 767, 740, 710, 674; 1H NMR (400 MHz,
CDCl3)
d
: 1.23–1.43 (m, 3H), 1.69 (d, J¼12.4 Hz, 1H), 1.78–1.89 (m,
4H), 2.24–2.35 (m, 2H), 3.27 (s, 2H), 4.03–4.15 (m, 1H), 7.00 (dd,
J¼8.0, 2.0 Hz, 1H), 7.21 (d, J¼2.0 Hz, 1H), 7.30 (d, J¼8.0 Hz, 1H);
13C NMR (100 MHz, CDCl3)
d: 25.4, 26.5, 30.1, 33.8, 61.2, 119.8, 123.6,
Acknowledgements
124.9, 129.5, 132.4, 141.5, 166.8; MS (EI) m/z: 281 (Mþ, 27%), 199
This work was supported by grants from SMBA-Korea (2007-
S1016568).
(100), 170 (27), 154 (18), 55 (7).
4.2.12. 6-Chloro-4-((tetrahydrofuran-2-yl)methyl)-2H-
benzo[b][1,4]thiazin-3(4H)-one (3l)
References and notes
A light-yellow oil; IR (KBr)
1675, 1581, 1560, 1475, 1415, 1347, 1308, 1255, 1137, 1105, 1081,1014,
942, 807, 780, 730, 676; 1H NMR (400 MHz, CDCl3)
: 1.57–1.66 (m,
n
/cmꢁ1: 3091, 3070, 2973, 2920, 2872,
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