An efficient synthetic protocol for quinoxalinones, Benzoxazinones, and benzothiazinones from 2-oxo-2-aryl-acetyl bromide precursors

Article abstract of DOI:10.1002/jhet.1557

α-Bromoketones undergo selenium dioxide oxidation to yield reactive 2-oxo-2-arylacetyl bromides that are trapped by aryl-1,2-diamines, 1,2-aminophenol or 1,2-aminothiophenol to give quinoxalinones, benzoxazinones, and benzothiazinones, respectively, in go

Full text of DOI:10.1002/jhet.1557

Month 2013 An Efficient Synthetic Protocol for Quinoxalinones, Benzoxazinones, and
Benzothiazinones from 2-Oxo-2-aryl-acetyl Bromide Precursors
Muthupandi Nagaraj, Sithuraj Sathiyamoorthy, Muthusamy Boominathan, Shanmugam Muthusubramanian,
and Nattamai Bhuvaneshb
a
a
a
a
*
aDepartment of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, India
bX-ray Diffraction Lab, Department of Chemistry, Texas A&M University, College Station, TX 77842, USA
*
E-mail: muthumanian2001@yahoo.com
Additional Supporting Information may be found in the online version of this article.
Received August 11, 2011
DOI 10.1002/jhet.1557
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
R3
XH
X
N
O
R3
O
R2
O
NH2
R1
Br
Br
SeO2 /dioxane
Ar
R2
Ar
MW/ 120 °C / 3 min
Ar
Stirring, RT
O
R1
X = NH, S, O
2 - 5 Min
a-Bromoketones undergo selenium dioxide oxidation to yield reactive 2-oxo-2-arylacetyl bromides that
are trapped by aryl-1,2-diamines, 1,2-aminophenol or 1,2-aminothiophenol to give quinoxalinones, benzox-
azinones, and benzothiazinones, respectively, in good yield.
J. Heterocyclic Chem, 00 00 (2013).
INTRODUCTION
with glyoxal/benzil/benzoyl formate [13]/1-phenyl propane-
1,2-dione [14]/phenacyl bromide followed by oxidation with
m-CPBA [15]. This article describes a simple protocol for
the synthesis of these classes of compounds.
Quinoxalinone core is commonly found in compounds
displaying a variety of medicinal properties, such as
antimicrobial, anticancer, anxiolytic, analgesic, antispastic,
antiallergic, and antithrombotic activities [1]. Quinoxali-
nones have been shown to exhibit the anxiolytic [2] and
neuroprotective activities [3] in human clinical testing.
Polymerase inhibitor A [4] has quinoxalinone entity, and
compound B [5,6] is used as a drug for cardiovascular
diseases (Fig. 1). Despite broad physiological significance
of this moiety, there are only few synthetic routes available
to this class of heterocycles [7]. Recently, quinoxalinones
have been synthesized by palladium-catalyzed intramolec-
ular N-arylations [8a], intramolecular copper-catalyzed
Ullmann-type reaction [8b], and Hinsberg reaction of
a-keto ester with aromatic 1,2-diamines [8c].
The related heterocyclic moieties having wide scope in
the area of photochemistry and photobiology are benz
[1,4]oxazin-2-ones and benz[1,4]thiazin-2-ones. Benzoxa-
zinone derivatives are a class of compounds exhibiting
spectral and photophysical properties of great interest [9].
Benzothiazinone derivative C exhibits bacteriostatic activ-
ity with respect to strains Staphylococcus aureus P-209
and Escherichia coli M17 [10], and the derivative D is
effective as an antitumour agent [11]. Because of their in-
tense fluorescence characteristics both in organic solutions
and crystalline state, the benzoxazinone derivatives are
employed as singlet oxygen sensitizers [12]. Previously,
these oxazinone/thiazinone moieties have been synthesized
by the condensation of 2-aminophenol/2-aminothiophenol
RESULTS AND DISCUSSION
All the synthetic routes reported for the synthesis of
quinoxalinones [16], benzoxazinones, and benzothiazi-
nones require longer reaction time, harsh conditions, metal
catalyst, and tedious work-up process. Realizing these
difficulties, a simple and efficient route to synthesize these
moieties in good yield from a novel precursor, arylacetyl
bromide 2, is envisaged.
Substituted phenacyl bromides 1 have been taken as the
precursors for the sequence of the reactions described in
this work. It can be pointed out that phenacyl bromide
reacted with 2-aminothiophenol to give 2H-benzothiazine
that was subsequently oxidized to give benzothiazinone
[15]. In the present investigation, we intend to use the
dicarbonyl compound ArCOCOBr, generated from phena-
cyl bromide, as the starting material to construct benzohe-
troazinone system. A survey on the reactions of phenacyl
bromide with oxidizing agents indicates that there is only
one report wherein 2-b-naphthyl acetyl bromide has been
subjected to selenium dioxide oxidation yielding, proba-
bly, the diketo compound. But the oxidized acetyl bromide
has not been isolated, only the respective ester has been
isolated and characterized [17]. No other method of gener-
ating ArCOCOBr could be traced. Realizing the longer
reaction time reported for the reaction of ArCOCH2Br with
© 2013 HeteroCorporation

M. Nagaraj, S. Sathiyamoorthy, M. Boominathan, S. Muthusubramanian, and N. Bhuvanesh
Vol 000
O
generated assisted by microwaves, and they have all been
allowed to react with different 1,2-difunctional aromatic
compounds to obtain a range of widely substituted quinoxa-
linones, benzoxazinones, and benzothiazinones (4).
O
H
O
N
H
N
N
N
N
N
H
N
O
N
H
O
Although it cannot be claimed as a one-pot reaction, the
whole reaction sequence is very simple and gets completed
within 10min, giving excellent yield of 4 (Table 1). The
compounds are all adequately characterized (see Supporting
Information). The structure of 4k has been unambiguously
confirmed by single crystal X-ray analysis (Fig.2) [18].
When 3,5-dimethylphenylenediamine is allowed to
react with 2-oxo-2-phenylacetyl bromide 2 (Ar═phenyl) or
2-oxo-2-(4-methylphenyl)acetyl bromide 2 (Ar═4-methyl-
phenyl), a mixture of regioisomeric 4 was obtained in almost
equal amount of the individual regiomers (Table 1, 4h and
4i) as evident from the NMR spectra of these compounds.
Unfortunately, it was not possible to separate these two
isomers in these two cases.
A: Polymerase inhibitor
B: Cardio vascular drug CHD:
P
P
CO
CO
O
H
H
N
N
O
N
O
O
S
O
CH3
CH3
C: Bacteriostatic agent
D: Antitumour agent
Figure 1. Some important heterocycles of biological significance. [Color figure
can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
An attempted one-pot reaction involving 1,2-phenylene-
diamine, phenacyl bromide, and selenium dioxide in the
expectation of getting the target heterocycle 4 was not
successful as 1,2-diamine immediately reacts with selenium di-
oxide yielding benzo[c][1,2,5]selenadiazole 5 (Scheme 2) [19].
Thus, the synthesis of a set of novel quinoxalinones,
benzoxazinones, and benzothiazinones has been achieved
from a potential precursor, 2-oxo-2-arylacetyl bromide,
which was obtained from substituted phenacyl bromide
by oxidation. The protocol is simple and less time-consum-
ing, resulting in very good yield of the target heterocycles.
selenium dioxide [17], we carried out the oxidation of phe-
nacyl bromide and its analogies 1 by selenium dioxide in
1,4-dioxane under microwave irradiation at 120ꢀC for
3 min to get 2-oxo-2-arylacetyl bromides 2 in good yield.
The compounds 2 are highly lachrymatory, and isolation
and characterization have been found difficult.
Nevertheless, the viscous 2-oxo-2-phenylacetyl bromide
1
(2, Ar═Ph) has been isolated and characterized by H and
13C NMR spectra. In all other cases, 2 has not been isolated
and used as such for subsequent transformation. To the
solution of dioxane containing the intermediate 2-oxo-2-
arylacetyl bromide 2, 1,2-phenylenediamine/2-aminothio-
phenol/2-aminophenol (3) was added and stirred well at
room temperature for a few minutes (Scheme 1). Solid
quinoxalinone/benzoxazinone /benzothiazinone (4) was
thrown out of the reaction medium, which was purified by
column chromatography. Eight 1,2-diketones have been
EXPERIMENTAL
All melting points were recorded in open capillaries and are
1
uncorrected. The H and 13C NMR spectra were recorded on a
Bruker 300 MHz spectrometer (Bruker, Fallanden, Switzerland)
in CDCl3/DMSO-d6 using TMS as internal standard. The chemi-
cal shifts are presented in d-scale. Elemental analyses were per-
formed on a Perkin Elmer 2400 series II Elemental CHNS
analyzer (Perkin Elmer, Lv Venlo, The Netherlands). Microwave
syntheses were carried out in CEM-DISCOVER model no.
908010 (CEM Corporation, Matthews, NC, USA). All chromato-
graphic separations were performed on a 60–120 mesh silica gel
using petroleum ether–ethyl acetate as eluent.
Scheme 1
O
O
Br
SeO2 /dioxane
MW/ 1200C / 3 min
Br
Ar
Ar
General procedure for the preparation of 2-oxo-2-phenyl
O
2
acetyl bromide (2a).
Selenium dioxide 0.55 g (0.005 mol)
1
was dissolved in dioxane (3.0mL) taken in a 10-mL microwave
vial. To this, phenacyl bromide 1.0 g (0.005 mol) was added, and
the reaction mixture was subjected to microwave irradiation
(CEM-DISCOVER model no. 908010) at 120ꢀC for 3min in
150 watts microwave power. Completion of the reaction was
confirmed by TLC. Data for 2a: This compound was obtained as
viscous oil; yield above 90%; 1H NMR (300MHz, CDCl3):
d = 7.48–7.66 (m, 3H), 8.16 (d, J = 7.2 Hz, 2H); 13C NMR
(75 MHz, CDCl3): d = 128.8, 130.5, 131.9, 135.2, 163.7, 185.6.
General procedure for preparation of quinoxalinone/
benzoxazinone/benzothiazinone (4). The generated 2-oxo-2-phenyl
R3
R2
XH
O
X
N
O
R3
R2
NH2
Br
Ar
R1
3
Ar
O
Stirring, RT
2 - 5 min
R1
X = NH, S, O
4
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Quinoxalinones, Benzoxazinones, and Benzothiazinones
Table 1
Synthesis of quinoxalinones, benzoxazinones, and benzothiazinones from 2-oxo-2-aryl acetyl bromides 2.
Entry
2
3
Product 4
Yield (%)
89
4a
4b
4c
4d
87
84
87
4e
4f
89
79
81
4g
4ha
4ia
82
78
4j
79
81
4k
4l
80
81
4m
4n
82
4o
4p
87
85
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Nagaraj, S. Sathiyamoorthy, M. Boominathan, S. Muthusubramanian, and N. Bhuvanesh
Vol 000
Table 1 (Continued)
Entry
Entry
2
3
Product 4
Yield (%)
4q
4r
82
81
4s
4t
87
86
82
4u
aMixture of isomers was obtained.
Figure 2. ORTEP diagram of compound 4k. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
239ꢀC [8c]); IR: NH 3095, CO 1665cmÀ1; H NMR (300MHz,
DMSO-d6): d = 7.29 (t, J = 7.5 Hz, 1H), 7.24 (d, J = 7.5Hz, 1H),
1
Scheme 2
N
7.43–7.52 (m, 4H), 7.85 (d, J = 7.5 Hz, 1H), 8.33 (d,
J = 7.8Hz, 2H), 12.4 (s, 1H); 13C NMR (75 MHz, DMSO-d6):
Se
SeO2/ dioxane
N
O
d = 113.7, 121.8, 126.3, 127.3, 128.6, 129.3, 130.6, 130.7, 132.8,
134.1, 151.2, 153.3; Anal. Calcd for C14H10N2O: C, 75.66; H,
NH2
NH2
5
Br
4.54; N, 12.60. Found: C, 75.45; H, 4.61; N, 12.43.
H
N
3-(4-Methylphenyl)quinoxalin-2(1H)-one (4b). This compound
O
was obtained as straw yellow color solid; mp> 250ꢀC; IR: NH
1
3112, CO 1668 cmÀ1; H NMR (300 MHz, DMSO-d6): d = 2.30
SeO2/ dioxane
N
(s, 3H), 7.21 (d, J = 8.1 Hz, 2H), 7.28 (t, J = 7.8 Hz, 1H), 7.33
(d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.78 (d, J = 7.8 Hz,
1H), 8.23 (d, J = 8.1 Hz, 2H), 12.4 (s, 1H); 13C NMR (75MHz,
DMSO-d6): d = 18.6, 111.8, 113.7, 121.8, 127.2, 128.0,* 129.7,
130.5, 131.1, 138.8, 149.9, 153.8; Anal. Calcd for C15H12N2O: C,
76.25; H, 5.12; N, 11.86. Found: C, 76.08; H, 4.99; N, 11.92.
* Two carbons merged together.
acetyl bromide 2 in dioxane was stirred with equimolar amount of
o-phenylenediamine/2-aminophenol/2-aminothiophenol for 2–5min.
The isolated solid quinoxalinone/benzoxazinone/benzothiazinone
was purified by column chromatography from petroleum ether
and ethyl acetate mixture (98:2).
3-(4-Methoxyphenyl)quinoxalin-2(1H)-one (4c).
This
compound was obtained as straw yellow color solid; mp> 250ꢀC;
1
IR: NH 3117, CO 1667cmÀ1; H NMR (300 MHz, DMSO-d6):
3-Phenylquinoxalin-2(1H)-one (4a).
This compound was
obtained as straw yellow color solid; mp > 250ꢀC (Lit. mp 237–
d = 3.86 (s, 3H), 6.97 (d, J = 8.1Hz, 2H), 7.28 (t, J = 7.8 Hz, 1H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Quinoxalinones, Benzoxazinones, and Benzothiazinones
7.33 (d, J = 7.8Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.78 (d, J = 7.8Hz,
1H), 8.41 (d, J = 8.1 Hz, 2H), 12.4 (s, 1H); 13C NMR (75 MHz,
DMSO-d6): d = 53.8, 111.8, 113.7, 121.8, 127.2, 128.0,* 129.7,
130.5, 131.1, 152.0, 153.8, 159.8; Anal. Calcd for C15H12N2O2:
C, 71.42; H, 4.79; N, 11.10. Found: C, 71.28; H, 4.65; N, 10.95.
* Two carbons merged together.
3-(3-Nitrophenyl)-2H-benzo[b][1,4]oxazin-2-one (4l). This
compound was obtained as colorless solid; mp 165–167ꢀC; IR:
1
CO 1746, NO2 1691, 1397 cmÀ1; H NMR (300 MHz, CDCl3):
d = 7.38 (d, J = 8.1 Hz, 1H), 7.45 (t, J = 7.8 Hz, 1H), 7.60 (t,
J = 7.8 Hz, 1H), 7.69 (t, J = 8.1 Hz, 1H), 7.91 (d, J = 7.8Hz, 1H),
8.38 (d, J = 8.1 Hz, 1H) 8.78 (d, J = 7.8Hz, 1H), 9.24 (s, 1H); 13C
NMR (75 MHz, CDCl3): d = 116.3, 124.4, 125.6, 125.9, 129.4,
129.8, 131.3, 132.2, 135.1, 135.5, 146.6, 148.1, 148.4, 151.9;
Anal. Calcd for C14H8N2O4: C, 62.29; H, 3.01; N, 10.44. Found:
C, 62.18; H, 2.92; N, 10.51.
3-(4-Chlorophenyl)quinoxalin-2(1H)-one (4d). This
compound was obtained as straw yellow color solid; mp > 250ꢀC;
1
IR: NH 3103, CO 1668cmÀ1; H NMR (300MHz, DMSO-d6):
d = 7.30 (t, J = 7.5 Hz, 1H), 7.36 (d, J = 7.5Hz, 1H), 7.43–7.50
(m, 3H), 7.80 (d, J = 7.5Hz, 1H), 8.41 (d, J = 8.4 Hz, 2H), 12.62
(s, 1H); 13C NMR (75MHz, DMSO-d6): d = 113.7, 121.8, 126.3,
127.3, 128.6, 129.3, 130.6, 130.7, 132.8, 134.1, 151.2, 153.3;
Anal. Calcd for C14H9ClN2O: C, 65.51; H, 3.53; N, 10.91. Found:
C, 65.38; H, 3.65; N, 10.82.
3-(4-Nitrophenyl)-2H-benzo[b][1,4]oxazin-2-one (4m). This
compound was obtained as colorless solid; mp 182–184ꢀC; IR:
1
CO 1746, NO2 1695, 1393 cmÀ1; H NMR (300MHz, CDCl3):
d = 7.36 (dd, J = 8.1 Hz, 1.2 Hz, 1H), 7.45 (td, J = 8.1Hz, 1.2 Hz,
1H), 7.61 (td, J = 8.1 Hz, 1.2 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H),
8.31 (d, J = 9.0 Hz, 2H) 8.56 (d, J = 9.0 Hz, 2H); 13C NMR
(75 MHz, CDCl3): d = 116.3, 123.3, 125.9, 129.2, 129.9, 131.4,
132.4, 139.5, 146.5, 148.3, 149.2, 151.8; Anal. Calcd for
C14H8N2O4: C, 62.29; H, 3.01; N, 10.44. Found: C, 62.14; H,
2.88; N, 10.38.
3-(4-Bromophenyl)quinoxalin-2(1H)-one (4e).
compound was obtained as straw yellow color solid;
mp > 250ꢀC; IR: NH 3083, CO 1662 cmÀ1 1H NMR
This
;
(300 MHz, DMSO-d6): d = 7.30 (t, J = 7.5 Hz, 1H), 7.36 (d,
J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.60 (d, J = 6.9 Hz,
2H), 7.82 (d, J = 7.5 Hz, 1H), 8.32 (d, J = 6.9 Hz, 2H), 12.51 (s,
1H); 13C NMR (75 MHz, DMSO-d6): d = 113.8, 121.9, 122.8,
128.9, 129.3, 129.6, 130.6, 130.8, 133.3, 134.1, 151.4, 153.4;
Anal. Calcd for C14H9BrN2O: C, 55.84; H, 3.01; N, 9.30.
Found: C, 55.69; H, 3.14; N, 9.16.
3-(4-Bromophenyl)-2H-benzo[b][1,4]oxazin-2-one (4n). This
compound was obtained as colorless solid; mp 160–162ꢀC; IR: CO
1
1749 cmÀ1; H NMR (300 MHz, CDCl3): d = 7.32 (d, J= 7.8Hz,
1H), 7.40 (td, J = 7.8 Hz, 1.5 Hz, 1H), 7.53 (td, J=7.8Hz, 1.5Hz,
1H), 7.61 (d, J=8.7Hz, 2H), 7.83 (dd, J=7.8Hz, 1.5Hz, 1H), 8.25
(d, J= 8.7 Hz, 2H);13C NMR (75 MHz, CDCl3): d = 116.2, 125.6,
129.5, 130.9, 131.4, 131.5, 131.6, 131.9, 132.9, 146.5, 149.5, 152.0;
Anal. Calcd for C14H8BrNO2: C, 55.66; H, 2.67; N, 4.64. Found: C,
55.42; H, 2.54; N, 4.49.
6,7-Dimethyl-3-phenylquinoxalin-2(1H)-one (4f). This
compound was obtained as straw yellow color solid; mp > 250ꢀC;
1
IR: NH 3102, CO 1660cmÀ1; H NMR (300MHz, DMSO-d6):
d = 2.32 (s, 3H), 2.34 (s, 3H), 7.10 (s, 1H), 7.21–7.28 (m, 3H), 8.25
(d, J= 8.4 Hz, 2H), 12.34 (s, 1H); 13C NMR (75 MHz, DMSO-d6):
d = 17.3, 18.2, 113.8, 121.9, 122.8, 128.9, 129.3, 129.6, 130.6,
130.8, 133.3, 134.1, 151.4, 153.4; Anal. Calcd for C16H14N2O: C,
76.78; H, 5.64; N, 11.19. Found: C, 76.64; H, 5.53; N, 11.23.
3-(4-Bromophenyl)-6,7-dimethylquinoxalin-2(1H)-one (4g). This
compound was obtained as straw yellow color solid; mp > 250ꢀC; IR:
NH 3123, CO 1669 cmÀ1; 1H NMR (300 MHz, DMSO-d6): d =2.31
(s,3H), 2.33 (s, 3H), 7.09 (s, 1H), 7.54 (s, 1H), 7.58 (d, J= 8.4 Hz, 2H),
8.30 (d, J=8.4Hz, 2H), 12.46 (s, 1H); 13C NMR (75 MHz, DMSO-
d6): d = 17.7, 18.6, 113.9, 122.4, 127.2, 128.8, 129.3, 129.5, 130.7,
130.8, 133.6, 138.8, 149.9, 153.4; MS: m/z 328.9 (M+); Anal. Calcd
for C16H13BrN2O: C, 58.38; H, 3.98; N, 8.51. Found: C, 58.46; H,
3-(Naphthalen-2-yl)-2H-benzo[b][1,4]oxazin-2-one (4o). This
compound was obtained as colorless solid; mp 127–129ꢀC; IR: CO
1
1747 cmÀ1; H NMR (300 MHz, CDCl3): d =7.33 (td, J=8.4Hz,
J= 1.2 Hz, 1H), 7.39 (dd, J=7.5Hz, J= 1.2 Hz, 1H), 7.47–7.57 (m,
3H), 7.84–7.92 (m, 3H), 7.97 (d, J= 7.5 Hz, 1H), 8.37 (d,
J= 8.4 Hz, 1H), 9.04 (s, 1H); 13C NMR (75 MHz, CDCl3):
d = 116.1, 125.3, 125.5, 126.4, 127.5, 127.9, 128.0, 129.4, 129.6,
131.0, 131.1, 131.4, 131.8, 132.8, 134.6, 146.4, 150.1, 152.3; Anal.
Calcd for C18H11NO2: C, 79.11; H, 4.06; N, 5.13. Found: C, 79.22;
H, 4.09; N, 5.06.
3-(5-Bromothiophen-2-yl)-2H-benzo[b][1,4]oxazin-2-one (4p). This
compound was obtained as colorless solid; mp 90–92ꢀC; IR: CO
1
1749 cmÀ1; H NMR (300 MHz, CDCl3): d =7.10 (d, J= 4.2 Hz, 1H)
4.02; N, 8.62.
7.26 (d, J= 8.1 Hz, 1H), 7.36 (td, J=8.1Hz, J= 1.5 Hz, 1H), 7.49 (dd,
J=8.1Hz, J= 1.5 Hz, 1H), 7.72 (d, J= 8.1 Hz, 1H), 8.10 (d, J=8.1Hz,
1H); 13C NMR (75MHz, CDCl3): d = 116.2, 121.1, 125.7, 128.8, 130.6,
131.4, 131.5, 133.3, 139.8, 144.4, 145.8, 151.2; Anal. Calcd for
C12H6BrNO2S: C, 46.77; H, 1.96; N, 4.55; S, 10.41. Found: C, 46.59; H,
3-Phenyl-2H-benzo[b][1,4]oxazin-2-one (4j). This
compound was obtained as colorless solid; mp 124–126ꢀC; IR: CO
1
1741 cmÀ1; H NMR (300 MHz, CDCl3): d =7.29 (dd, J=7.8Hz,
J = 1.5 Hz, 1H), 7.35 (td, J = 7.8 Hz, J = 1.5 Hz, 1H), 7.44–7.54
(m, 4H), 7.81 (dd, J = 7.8 Hz, J = 1.5 Hz, 1H), 8.31 (d,
J = 5.7 Hz, J = 1.5 Hz, 2H); 13C NMR (75 MHz, CDCl3):
d = 116.0, 125.4, 128.3, 129.3,* 131.0, 131.3, 131.5, 134.0,
146.3, 150.7, 152.1; MS: m/z 224.0 (M+); Anal. Calcd for
C14H9NO2: C, 75.33; H, 4.06; N, 6.27. Found: C, 75.25; H,
4.11; N, 6.30.* Two carbons merged here.
2.03; N, 4.62; S, 10.34.
3-Phenyl-2H-benzo[b][1,4]thiazin-2-one (4q). This compound
was obtained as colorless solid; mp 109–111ꢀC; IR: CO
1
1637cmÀ1; H NMR (300 MHz, CDCl3): d = 7.36 (t, J = 7.8 Hz,
1H), 7.46–7.54 (m, 4H), 7.87 (d, J = 7.8 Hz, 1H), 8.06–8.09 (m,
3H); 13C NMR (75MHz, CDCl3): d = 121.6, 123.2, 125.1, 126.2,
127.5, 128.9, 130.9, 131.3, 133.6, 135.0, 154.1, 168.0; Anal.
Calcd for C14H9NOS: C, 70.27; H, 3.79; N, 5.85; S, 13.40.
Found: C, 70.16; H, 3.84; N, 5.78; S, 13.32.
3-(4-Methylphenyl)-2H-benzo[b][1,4]oxazin-2-one (4k). This
compound was obtained as colorless solid; mp 110–112ꢀC; IR:
CO 1743 cmÀ1 1H NMR (300MHz, CDCl3): d = 2.42 (s, 3H),
;
7.25–7.34 (m, 3H), 7.38 (dd, J = 7.8Hz, J = 1.2 Hz, 1H), 7.48 (td,
J = 7.8Hz, J = 1.2Hz, 1H), 7.81 (dd, J = 7.8Hz, J = 1.2 Hz, 1H),
8.24 (d, J = 8.1Hz, 2H); 13C NMR (75 MHz, CDCl3): d =21.6,
116.0, 125.4, 129.1, 129.3, 129.4, 130.7, 131.4, 131.7, 141.9,
146.3, 150.6, 152.3; Anal. Calcd for C15H11NO2: C, 75.94; H,
4.67; N, 5.90. Found: C, 75.85; H, 4.61; N, 5.82.
3-(4-Methylphenyl)-2H-benzo[b][1,4]thiazin-2-one (4r). This
compound was obtained as colorless solid; mp 110–112ꢀC; IR: CO
1639 cmÀ1; 1H NMR (300 MHz, CDCl3): d = 2.38 (s, 3H), 7.25 (d,
J= 8.1 Hz, 2H), 7.35 (td, J=7.8Hz, J=1.2Hz, 1H), 7.45 (td,
J=7.8Hz, J= 1.2 Hz, 1H), 7.84 (d, J= 7.8 Hz, 1H), 7.95 (d,
J= 8.1Hz, 2H), 8.04 (d, J= 8.1 Hz, 1H); 13C NMR (75MHz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Nagaraj, S. Sathiyamoorthy, M. Boominathan, S. Muthusubramanian, and N. Bhuvanesh
Vol 000
Molecules 2000, 5, 864; d) Li, X.; Yang, K.; Li, W.; Xu, W. Drugs Future
2006, 31, 979. e) Carta, A.; Piras, S.; Loriga, G.; Paglietti, G. Mini Rev
Med Chem 2006, 6, 1179.
[2] Tang, A. H.; Franklin, S. R.; Hmes, C. S.; Ho, P. M. J Pharmacol
Exp Ther 1991, 259, 248.
[3] Takahashi, M.; Ni, J. W.; Yatsugi, S. K.; Toya, T.; Yatsugi, S.
I.; Sasamata, M. S.; Koshiya, K.; Shishikura, J. I.; Sakamoto, S.;
Yamagouchi, T. J Pharmacol Exp Ther 1998, 284, 467.
[4] Mabire, D. J. P. et al. US patent 7879857B2. 2011.
[5] Ergüden et al. US patent 0247244A1, 2006.
CDCl3): d = 21.4, 121.4, 122.9, 124.9, 126.1,* 127.4, 129.6, 130.9,
134.9, 141.3, 154.1, 168.1; MS: m/z 254.2 (M+); Anal. Calcd for
C15H11NOS: C, 71.12; H, 4.38; N, 5.53; S, 12.66. Found: C,
70.23; H, 4.25; N, 5.48; S, 12.59; * Two carbons merged here.
3-(3-Nitrophenyl)-2H-benzo[b][1,4]thiazin-2-one (4s).
compound was obtained as colorless solid; mp 157–159ꢀC; IR:
CO 1633 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.44 (td,
This
;
J = 7.5Hz, J = 0.9Hz, 1H), 7.56 (td, J = 7.5 Hz, J = 0.9 Hz, 1H),
7.67 (t, J = 8.1 Hz, 1H), 7.69 (d, J = 7.5Hz, 1H), 8.10
(d, J =8.1 Hz, 1H), 8.33 (dd, J = 8.1 Hz, J = 0.9 Hz, 1H), 8.40 (dd,
J = 7.5Hz, J = 0.9 Hz, 1H), 9.24 (d, J = 0.9Hz, 1H); 13C NMR
(75 MHz, CDCl3): d = 121.8, 122.3, 122.8, 123.7, 125.1, 126.0,
126.8, 130.0, 132.9, 135.2, 135.3, 148.8, 153.9, 164.8; Anal.
Calcd for C14H8N2O3S: C, 59.15; H, 2.84; N, 9.85; S, 11.28.
Found: C, 59.06; H, 2.92; N, 9.73; S, 11.19.
[6] Smith C. D.; Lawrence D. S. US patent 6815442, 2004.
[7] a) Zaragoza, F.; Stephensen, H. J Org Chem 1999, 64,
ꢀ
2555; b) Krchnák, V.; Szabo, L.; Vágner, J. Tetrahedron Lett 2000,
41, 2835; c) Patel, M.; Mchugh, R. J.; Cordova, B. C.; Klabe, R.
M.; Viitanen, S. E.; Trainor G. L.; Rodgers, J. D. Bioorg Med Chem
Lett 2000, 10, 1729; d) Dudash, J.; Zhang, Y.; Moore, J. B.; Look,
R.; Liang, Y.; Beavers, M. P.; Conway, B. R.; Rybczynski P. J.;
Demarest, K. T. Bioorg Med Chem Lett 2005, 15, 4790; e) Kotb,
E. R.; Anwar, M. A.; Soliman, M. S.; Salama, M. A. Phosphorus,
Sulfur, and Silicon 2007, 182, 1119; f) Gris, J.; Glisoni, R.; Fabian,
L.; Fernández, B.; Moglioni, A G. Tetrahedron Lett 2008, 49, 1053;
g) Xue, Z. Y.; Jiang, Y.; Peng, X. Z.; Yuan, W.C.; Zhang, X.M.
Adv Synth Catal 2010, 352, 2132.
[8] a) Luo, X.; Chenard, E.; Martens, P.; Cheng, Y. X.;
Tomaszewski, M. J. Org Lett 2010, 12, 3574; b) Vaillard, V. A.;
Rossi, R. A.; Martın, S. E. Org Biomol Chem 2011, 9; 4927. c)
Murthy, S. N.; Madhav, B.; Nageswar,Y. V. D. Helv Chim Acta
2010, 93, 1216.
[9] a) Le Bris, M. T. J Heterocycl Chem 1984, 21, 551; b) Nishio,
T.; Omote, Y. J Org Chem 1985, 50, 1370; c) Nishio, T. J. Chem. Soc.,
Perkin Trans. 1990, 1, 565. d) Nonell, S.; Ferreras, L. R.; Cañete, A.;
Lemp, E.; Günther, G.; Pizzaro, N.; Zanocco, A. L. J Org Chem 2008,
73, 5371.
[10] Kozminykh, V. O.; Igidov, N. M.; Kozminykh, E.; Russsian,
N. J Org Chem 2003, 39, 863.
[11] Sengupta, S. K.; Trites, D. H.; Madhavarao, M. S.; Beltz, W.
R. J Med Chem 1979, 22, 797.
3-(Naphthalen-2-yl)-2H-benzo[b][1,4]thiazin-2-one (4t). This
compound was obtained as colorless solid; mp 165–167ꢀC; IR: CO
1
1641 cmÀ1; H NMR (300 MHz, CDCl3): d =7.39 (td, J=7.5Hz,
J= 1.8 Hz, 1H), 7.47–7.55 (m, 3H), 7.85–7.97 (m, 4H), 8.10 (d,
J= 8.4 Hz, 1H), 8.20 (dd, J=8.4Hz, J= 1.5 Hz, 1H), 8.55 (s, 1H);
13C NMR (75 MHz, CDCl3): d = 121.6, 123.5, 124.4, 125.2, 126.3,
126.8, 127.4, 127.6, 127.8,* 128.8, 131.0, 133.2, 134.6, 135.2,154.3,
168.1; Anal. Calcd for C18H11NOS: C, 74.72; H, 3.83; N, 4.84; S,
11.08. Found: C, 74.68; H, 3.79; N, 4.79; S, 10.97.
3-(5-Bromothiophen-2-yl)-2H-benzo[b][1,4]thiazin-2-one
(4u).
This compound was obtained as colorless solid; mp
89–91ꢀC; IR: CO 1642 cmÀ1
;
1H NMR (300 MHz, CDCl3):
d = 7.20 (d, J = 5.2 Hz, 1H) 7.50–7.61 (m, 2H), 7.98 (d,
J = 7.8 Hz, 1H), 8.20 (d, J = 7.8 Hz, 1H), 8.37 (d, J = 5.2 Hz,
1H); 13C NMR (75 MHz, CDCl3): d = 122.2, 125.5, 126.4,
127.7, 131.3, 131.5, 134.9, 137.8, 140.3, 153.5, 165.9,
175.4; Anal. Calcd for C12H6BrNOS2: C, 44.45; H, 1.87; N,
4.32; S, 19.78. Found: C, 44.59; H, 1.78; N, 4.28; S, 19.82.
[12] a) Le Bris, M. T. J Heterocycl Chem 1985, 22, 1275. b)
Cañete, A.; Lemp, E.; Günther, G.; Pizzaro, N.; Zanocco, A. L. J
Photochem Photobiol A Chem 2008, 199, 345.
[13] Le Bris, M. T. J Heterocycl Chem 1989, 26, 429.
[14] Santes, V.; Lima, S. R.; Santillan, R. L.; Farfán, N.
Monatshefte für Chemie 1999, 130, 1481.
[15] Sabatini, S.; Kaatz, G.W.; Rossolini, G. M.; Brandini, D.;
Fravolini, A. J Med Chem 2008, 51, 4321.
Acknowledgments. The authors thank DST, New Delhi for
assistance under the IRHPA program for the NMR facility.
One of the authors (M.N) thanks CSIR, New Delhi for a
Junior Research Fellowship.
[16] Krchnák, V.; Szabo, L.; Vágner, J. Tetrahedron Lett 2000, 41,
2835.
REFERENCES AND NOTES
[17] Kotb, E. R.; Anwer, M. A.; Soliman, M. S.; Salama, M.A.
Phosphorus Sulfur Silicon 2007, 182, 1119.
[18] CCDC No: 832083.
[19] Zhu, B.; Zhang, X.; Jia, H.; Li, Y.; Liu, H.; Tan, W. Org
Biomol Chem 2010, 8, 1650.
[1] a) Kinashi, H.; Otten, S. L.; Dunkan, J. S.; Hutchinson, C. R. J
Antibiot 1988, 41, 642; b) Sarges, R.; Howard, H.R.; Browne, R.C.;
Label, L.A.; Seymour, P.A. J Med Chem 1990, 33, 2240; c) Ali, M. M.
M.; Ismail, M. F.; Elgaby, M. S. A.; Zahran, M. A.; Ammar, Y. A.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet