Phl(OAc)2-mediated one-pot synthesis of benzoxazinones from anthranilic acids and aromatic aldehydes

Article abstract of DOI:10.3184/174751912X13285455672357

A novel way to synthesise 2-aryl-4H-benzo[d][1,3]oxazin-4-ones has been developed by the cyclisation of Schiff bases with (diacetoxyiodo)benzene. The salient features of this new protocol which starts from an anthranilic acid and an aromatic aldehyde, are

Full text of DOI:10.3184/174751912X13285455672357

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 123
MARCH, 123–126
PhI(OAc)2-mediated one-pot synthesis of benzoxazinones from
anthranilic acids and aromatic aldehydes
Yuanyuan Xie* and Suping Wang
Key Laboratory for Green PharmaceuticalTechnologies and Related Equipment of Ministry of Education, College of Pharmaceutical
Sciences, Zhejiang University ofTechnology, Hangzhou 310014, P. R. China
A novel way to synthesise 2-aryl-4H-benzo[d][1,3]oxazin-4-ones has been developed by the cyclisation of Schiff
bases with (diacetoxyiodo)benzene. The salient features of this new protocol which starts from an anthranilic acid
and an aromatic aldehyde, are short reaction time, mild reaction conditions and good yields.
Keywords: benzoxazinones, hypervalent iodine, Schiff base, cyclisation
The benzoxazinone scaffold has been widely investigated in
medicinal chemistry over the last two decades.1–3 Benzoxazi-
none derivatives play an important role in the defence of the
human body against infections. Substituted 4H-benzo[d]
[1,3]oxazin-4-ones have been well characterised as heterocy-
clic acylating agents of serine proteases.4 Teshima et al. first
reported this class of alternative substrate inhibitors in 1982
and demonstrated that they were potent irreversible inhibitors
for human leukocyte elastase, porcine pancreatic elastase,
cathepsin G, and chymotrypsin.5 Since then there has been
considerable interest in the development of the inhibitory
effects of benzoxazinones.
Generally, the most common method for the synthesis of
benzoxazinones involves reaction of an anthranilic acid and an
acyl choride followed by dehydration6–8 (Scheme 1a). Recently
the microwave-assisted cyclocarbonylation of aryl iodides
(Scheme 1b) has been reported.9 The disadvantages of these
two reactions are that drastic and inconvenient conditions
are required and low yields are achieved. Here, we report a
novel one-pot protocol for the synthesis of benzoxazinones
from anthranilic acid, aromatic aldehyde and (diacetoxyiodo)
benzene [PhI(OAc)2] (Scheme 1c).
During the past several decades, the chemistry of polyvalent
iodine reagents has experienced an explosive development.
Furthermore, many synthetic reactions using hypervalent
iodine reagents have also been developed.10,11 There has been
an upsurge of interest in PhI(OAc)2 one of the classical hyper-
valent iodine reagents, mainly due to its very useful oxidising
properties, allied to its mild, highly selective, environmentally
benign, and commercial availability properties.12,13 We now
propose a novel preparation of benzoxazinones by the cyclisa-
tion of a Schiff base in the presence of PhI(OAc)2 (Scheme 2).
This is an important improvement in the application of
PhI(OAc)2.
The first step in the one-pot preparation of benzoxazinones
is the formation at 110 °C of a Schiff base from an anthranilic
acid and an aromatic aldehyde. The second step is the Schiff
base is directly oxidised by PhI(OAc)2, generating the cyclic
benzoxazinones.
2-Phenyl-4H-benzo[d][1,3]oxazin-4-one (4a) was chosen
as a candidate to optimise the reaction conditions in the second
step. Initially, several solvents such as toluene, dichlorometh-
ane, MeCN, MeOH and N,N-dimethylformamide (DMF) were
tested. The yield (83%) was observed in MeCN (Table 1,
entries 1–5). According to the proposed mechanism
(Scheme 3), acetic acid was produced as a by-product which,
it was concluded, might slow down the reaction. Accordingly,
a weak base such as Et3N or NaHCO3 was added to neutralise
the reaction system.14 However, the yields were not markedly
improved (entries 6 and 7). Additionally, 1.0 equiv. 2,2,6,6-
tetramethylpiperidine-1-oxyl (TEMPO) was tried as oxidant
with 0.5 equiv. PhI(OAc)2 as catalyst,15 but this failed to
improve the yield (entry 8). Furthermore, the effects of reac-
tion temperature and time were also taken into consideration
(entries 9 and 10) and it was found that a similar yield was
afforded by reducing the reaction time from 60 min to 30 min.
Finally the effect of the amount of PhI(OAc)2 was investigated
(entries 10–12), and a slightly higher yield was obtained
by using 1.1 equiv. PhI(OAc)2. On the basis of these results,
the reaction was carried out under the optimised reaction
conditions, namely, in MeCN at room temperature for 30 min
(entry 11).
Having established the optimised conditions, various anthra-
nilic acids and aromatic aldehydes were screened to explore
Scheme 1 Synthesis of benzoxazinones.
* Correspondent. E-mail: pharmlab@zjut.edu.cn

124 JOURNAL OF CHEMICAL RESEARCH 2012
Scheme 2
Table 1 Optimisation of reaction conditions
result was observed when 3-methylanthranilic acid was used
(entries 9–12). However, when 4-chloroanthranilic acid was
tested low yields were obtained for benzaldehydes carrying
electron-donating groups compared to its nonsubstituted
analogue (entries 13–15), and the reaction failed for benzalde-
hydes carrying electron-withdrawing groups (entries 16 and
17). The reason for this result was unclear.
In addition, in order to widen the scope of the reaction,
anthraldehyde and butyraldehyde were also investigated.
However, none of the desired product was observed.
Based on the results described, a plausible reaction mecha-
nism is depicted as follows (Scheme 3). Firstly, the reaction of
Schiff base (A) and PhI(OAc)2 affords the iodo complex (B)
and 1 mole of AcO−. The resulting AcO− abstracts a hydrogen
from the acid prompting cyclisation to form a six-membered
ring intermediate (C). Subsequently, AcOH and PhI are spon-
taneously eliminated from intermediate (C) to generate the
corresponding product benzoxazinone (D).
Entry PhI(OAc)2 Solvent
/equiv.
Additive
Temp. Time Yield
/°C /min /%a
1
2
1
PhMe
CH2Cl2
MeCN
MeOH
DMF
None
None
rt
rt
rt
rt
rt
rt
60
60
60
25
43
83
1
3
1
None
4
1
None
60 Trace
5
1
None
60
60
60
60
40
30
30
30
30
50
35
83
30
86
82
86
86
85
6
1
MeCN
Et3N(2equiv.)
7
1
MeCN NaHCO3(2equiv.) rt
MeCN TEMPO(1equiv.) rt
MeCN
MeCN
MeCN
MeCN
MeCN
8
0.5
1
9
None
None
None
None
None
60
rt
10
11
12
13
1
1.1
1.3
1.5
rt
rt
rt
a Isolated yield based on anthranilic acid.
In conclusion, we have developed a novel PhI(OAc)2-
mediated one-pot process to synthesise benzoxazinones from
anthranilic acids and benzaldehydes. A plausible mechanism
for the formation of benzoxazinones was proposed. Advan-
tages of this procedure are short reaction time, mild reaction
conditions and high yields. To the best of our knowledge such
a reaction is unprecedented and represents a completely new
route to benzoxazinones. Further extension of this method is
underway.
Table 2 Preparation of benzoxazinones
Entry
R1
R2
Product
Yield/%a
1
2
H
H
H
2-F
4-Me
2-Cl
2,4-diCl
4-Cl
4-F
4-Br
4-Me
3-MeO
2,4-diCl
4-F
3-MeO
4-MeO
H
4-Cl
4-F
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
86
81
3
H
85
4
H
86
5
H
84
6
H
85
7
H
84
8
H
88
9
3-Me
3-Me
3-Me
3-Me
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
87
Experimental
10
11
12
13
14
15
16
17
86
1H NMR and 13C NMR spectra were measured on a Varian 400
(400 MHz) spectrometer (chemical shifts in δ ppm) using TMS as
internal standard. Mass spectra (ESI-MS) were determined on a
Thermo Finnigan LCQ-Advantage. High resolution mass spectra
(ESI-HRMS) were determined on an Agilent 6210 TOF instrument.
Melting points were measured on a Büchi B-540 capillary melting
point apparatus.
85
86
68
66
83
Trace
Trace
a Isolated yield by column chromatography based on anthra-
nilic acid.
Synthesis of benzoxazinones; general procedure
To a solution of anthranilic acid (1 mmol) in toluene (20 mL) was
added aromatic aldehyde (1 mmol). The reaction mixture was heated
under reflux for 2 h. After removal of solvent by rotary evaporation,
the residue was dissolved in MeCN (5 mL) and PhI(OAc)2 (1.1 mmol,
0.354 g) was added. The reaction mixture was stirred at room tem-
perature for 30 min. After the completion of the reaction, the reaction
mixture was evaporated under vacuum. The residue was purified by
column chromatography (petroleum ether/ethyl acetate, 40:1) to
the substrate scope. The reaction results are listed in Table 2. It
was found that nonsubstituted anthranilic acid underwent the
reaction with benzaldehyde derivatives containing either an
electron-donating or electron-withdrawing group to obtain the
corresponding products in good yields (entries 1–8). A similar
Scheme 3

JOURNAL OF CHEMICAL RESEARCH 2012 125
3
afford a white solid. The six new components synthesised 4i–n have
been characterised by their spectral data.
(d, JCF = 9 Hz) (CH×2), 128.5, 128.1, 127.0, 126.2, 116.7, 115.9,
115.9 (d, 2JCF = 22 Hz) (CH×2) ppm; MS (ESI): m/z (%) = 242 (M++1,
100).
2-Phenyl-4H-benzo[d][1,3]oxazin-4-one (4a): White solid; m.p.
121.8–122.3 °C (lit.16 123–124 °C); IR (KBr): νmax = 3035, 1763,
2-(4-Bromophenyl)-4H-benzo[d][1,3]oxazin-4-one (4h): White solid;
m.p. 183.2–183.9 °C (lit.19 184 °C); IR (KBr): νmax = 2921, 1763,
1620, 1566, 1485, 1398, 1320, 1257, 1069, 1042, 1008, 833, 775 cm−1;
1H NMR (400 MHz, CDCl3): δ = 8.23 (dd, J1 = 1.6 Hz, J2 = 8.0 Hz,
1H, ArH), 8.17 (d, J = 8.4 Hz, 2H, ArH), 7.83 (td, J1 = 1.2 Hz, J2 =
7.6 Hz, 1H, ArH), 7.68 (d, J = 8.0 Hz, 1H, ArH), 7.64 (d, J = 8.4 Hz,
2H, ArH), 7.52 (t, J = 7.6 Hz, 1H, ArH) ppm; 13C NMR (100 MHz,
CDCl3): δ = 159.4 (C=O), 156.4 (C=N), 146.9, 136.8, 132.2 (CH×2),
129.9 (CH×2), 129.3, 128.8, 128.7, 127.9, 127.4, 117.2 ppm; MS
(ESI): m/z (%) =274 (100), 302 (M++1, 48) , 304 (M++3, 44).
8-Methyl-2-(4-methylphenyl)-4H-benzo[d][1,3]oxazin-4-one (4i):
White solid; m.p. 143.1–143.8 °C; IR (KBr): νmax = 2917, 1749, 1621,
1
1613, 1572, 1474, 1314, 1259, 1040, 1011, 764, 684 cm−1; H NMR
(400 MHz, CDCl3): δ = 8.29–8.31 (m, 2H, ArH), 8.23 (dd, J1 = 1.6 Hz,
J2 = 8.0 Hz, 1H, ArH), 7.82 (td, J1 = 1.6 Hz, J2 = 8.0 Hz, 1H, ArH),
7.69 (d, J = 8.0 Hz, 1H, ArH), 7.59–7.56 (m, 1H, ArH), 7.52–7.49 (m,
3H, ArH) ppm; 13C NMR (100 MHz, CDCl3): δ = 159.3 (C=O), 156.9
(C=N), 146.8, 136.4, 132.4, 130.1, 128.6 (CH×2), 128.4, 128.2
(CH×2), 128.1, 127.1, 116.9 ppm; MS (ESI): m/z (%) = 224 (M++1,
100).
2-(2-Fluorophenyl)-4H-benzo[d][1,3]oxazin-4-one (4b): White solid;
m.p. 113.4–114.1 °C (lit.16 115–116 °C); IR (KBr): νmax = 2922, 1770,
1628, 1455, 1316, 1277, 1222, 1107, 1037, 1007, 809, 756 cm−1;
1H NMR (400 MHz, CDCl3): δ = 8.25 (d, J = 7.6 Hz, 1H, ArH), 8.11
(td, J1 = 1.6 Hz, J2 = 7.6 Hz, 1H, ArH), 7.84 (t, J = 7.6 Hz, 1H, ArH),
7.71 (d, J = 8.0 Hz, 1H, ArH), 7.55 (t, J = 7.6 Hz, 2H, ArH), 7.28
(t, J = 8.0 Hz, 1H, ArH), 7.19–7.22 (m, 1H, ArH) ppm; 13C NMR
(100 MHz, CDCl3): δ = 161.1 (d, 1JCF = 258 Hz), 159.8 (C=O), 154.6
1
1598, 1311, 1240, 1176, 1048, 1019, 822, 761, 711 cm−1; H NMR
(400 MHz, CDCl3): δ = 8.20 (d, J = 8.4 Hz, 2H, ArH), 8.05 (d, J =
8.0 Hz, 1H, ArH), 7.64 (d, J = 7.6 Hz, 1H, ArH), 7.35 (t, J = 7.6 Hz,
1H, ArH), 7.29 (d, J = 8.0 Hz, 2H, ArH), 2.65 (s, 3H, CH3), 2.44
(s, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ = 160.0 (C=O),
155.7 (C=N), 145.1, 142.9, 137.0, 135.8, 129.2 (CH×2), 128.0
(CH×2), 127.6, 127.2, 125.9, 116.6, 21.8 (CH3), 17.2 (CH3) ppm; MS
(ESI): m/z (%) = 252 (M++1, 100); HRMS-ESI: Calcd for C16H14NO2
(M+1)+ 252.1025; found: 252.1015.
2-(3-Methoxyphenyl)-8-methyl-4H-benzo[d][1,3]oxazin-4-one
(4j): White solid; m.p. 119.3–120.1 °C; IR (KBr): νmax = 2960, 1741,
1621, 1584, 1481, 1311, 1267, 1216, 1058, 1004, 861, 773, 709 cm−1;
1H NMR (400 MHz, CDCl3): δ = 8.07 (d, J = 7.6 Hz, 1H, ArH), 7.93
(d, J = 7.6 Hz, 1H, ArH), 7.84–7.83(m, 1H, ArH), 7.66 (d, J = 7.2 Hz,
1H, ArH), 7.41 (t, J = 8.0 Hz, 1H, ArH), 7.38 (t, J = 8.0 Hz, 1H, ArH),
7.10 (dd, J1 = 2.0 Hz, J2 = 8.0, 1H, ArH), 3.91 (s, 3H, OCH3), 2.66 (s,
3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ = 159.8, 159.5 (C=O),
155.4 (C=N), 144.9, 137.1, 136.0, 131.6, 129.5, 127.5, 125.9, 120.6,
118.5, 116.7, 112.7, 55.5 (OCH3), 17.1 (CH3) ppm; MS (ESI): m/z (%)
= 268 (M++1, 100); HRMS-ESI: Calcd for C16H14NO3 (M+1)+
268.0974; found: 268.0965.
2-(2,4-Dichlorophenyl)-8-methyl-4H-benzo[d][1,3]oxazin-4-one
(4k): White solid; m.p. 162.8–163.4 °C; IR (KBr): νmax = 3072, 1764,
1625, 1585, 1472, 1373, 1322, 1222, 1112, 1079, 1029, 872, 800, 769
cm−1; 1H NMR (400 MHz, CDCl3): δ = 8.08 (d, J = 8.0 Hz, 1H, ArH),
7.96 (d, J = 8.4 Hz, 1H, ArH), 7.69 (d, J = 7.2 Hz, 1H, ArH), 7.56
(d, J = 2 Hz, 1H, ArH), 7.44 (t, J = 8.0 Hz, 1H, ArH), 7.38 (dd, J1 =
2.0 Hz, J2 = 8.4 Hz, 1H, ArH), 2.63 (s, 3H, CH3) ppm; 13C NMR
(100 MHz, CDCl3): δ = 159.4 (C=O), 153.5 (C=N), 144.6, 137.8,
137.4, 136.6, 134.6, 132.3, 131.2, 128.4, 128.2, 127.2, 126.0, 116.9,
17.3 (CH3) ppm; MS (ESI): m/z (%) = 306 (M++1, 100); HRMS-ESI:
Calcd for C15H10Cl2NO2 (M+1)+ 306.0089; found: 306.0080.
3
(C=N), 146.4, 136.4, 133.8 (d, JCF = 8 Hz), 130.9, 128.6, 128.4,
2
127.3, 124.2, 118.9, 117.2, 117.1 (d, JCF = 22 Hz), 116.8 ppm; MS
(ESI): m/z (%) = 242 (M++1, 100).
2-(4-Methylphenyl)-4H-benzo[d][1,3]oxazin-4-one (4c): White solid;
m.p. 152.1–153.2 °C (lit.17 154–155 °C); IR (KBr): νmax = 3036, 1759,
1
1609, 1570, 1474, 1310, 1261, 1183, 1063, 1040, 827, 769 cm−1; H
NMR (400 MHz, CDCl3): δ = 8.23–8.18 (m, 3H, ArH), 7.81 (t, J =
7.2 Hz, 1H, ArH), 7.67 (d, J = 8.0 Hz, 1H, ArH), 7.49 (t, J = 7.2 Hz,
1H, ArH), 7.31 (d, J = 8.0 Hz, 2H, ArH), 2.45 (s, 3H, CH3) ppm;
13C NMR (100 MHz, CDCl3): δ = 159.8 (C=O), 157.4 (C=N), 147.3,
143.5, 136.7, 129.7 (CH×2), 128.7, 128.5 (CH×2), 128.2, 127.6,
127.2, 117.1, 22.1 (CH3) ppm; MS (ESI): m/z (%) = 238 (M++1,
100).
2-(2-Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one (4d): White solid;
m.p. 137.3–138.1 °C (lit.17 139–140 °C); IR (KBr): νmax = 3081, 1768,
1625, 1475, 1440, 1315, 1272, 1223, 1092, 1029, 1003, 761, 730 cm−1;
1H NMR (400 MHz, CDCl3): δ = 8.27 (dd, J1 = 1.2 Hz, J2 = 8.0 Hz,
1H, ArH), 7.90–7.83 (m, 2H, ArH), 7.71 (d, J = 8.0 Hz, 1H, ArH),
7.60–7.56 (m, 1H, ArH), 7.52 (dd, J1 = 1.2 Hz, J2 = 8.0 Hz, 1H, ArH),
7.46 (td, J1 = 1.6 Hz, J2 = 7.2 Hz, 1H, ArH), 7.39 (td, J1 = 1.6 Hz,
J2 = 7.2 Hz, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3): δ = 159.0
(C=O), 156.3 (C=N), 146.3, 136.5, 133.3, 132.1, 131.3, 130.9, 130.2,
128.8, 128.4, 127.3, 126.7, 116.9 ppm; MS (ESI): m/z (%) = 258
(M++1, 100), 260 (M++3, 30).
2-(2,4-Dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one (4e): White
solid; m.p. 131.3–132.8 °C (lit.17 129–130 °C); IR (KBr): νmax = 3093,
1767, 1620, 1477, 1372, 1262, 1091, 1029, 1003, 858, 825, 772 cm−1;
1H NMR (400 MHz, CDCl3): δ = 8.25 (dd, J1 = 1.2 Hz, J2 = 8.0 Hz,
1H, ArH), 7.88 (d, J = 8.4 Hz, 1H, ArH), 7.85-7.83 (m, 1H, ArH), 7.70
(d, J = 8.0 Hz, 1H, ArH), 7.56-7.60 (m, 1H, ArH), 7.54(d, J = 2.0 Hz,
1H, ArH), 7.38 (dd, J1 = 2.0 Hz, J2 = 8.4 Hz, 1H, ArH) ppm; 13C NMR
(100 MHz, CDCl3): δ = 158.7 (C=O), 155.4 (C=N), 146.1, 137.9,
136.5, 134.3, 132.2, 131.0, 129.0, 128.6, 128.5, 127.3, 127.2, 116.8
ppm; MS (ESI): m/z (%) = 292 (M++1, 100), 294 (M++3, 62), 296
(M++5, 13).
2-(4-Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one (4f): White solid;
m.p. 189.3–190.1 °C (lit.17 190 °C); IR (KBr): νmax = 2926, 1769,
1624, 1603, 1489, 1403, 1323, 1259, 1223, 1095, 1058, 1024, 838,
761 cm−1; 1H NMR (400 MHz, CDCl3): δ = 8.27–8.24 (m, 3H, ArH),
7.87–7.82 (m, 1H, ArH), 7.69 (d, J = 8.4 Hz, 1H, ArH), 7.55 (dd,
J1 = 1.2 Hz, J2 = 8.4 Hz, 1H, ArH), 7.50 (d, J = 8.8 Hz, 2H, ArH) ppm;
13C NMR (100 Hz, CDCl3): δ = 159.1 (C=O), 156.0 (C=N), 146.6,
138.9, 136.5, 129.5 (CH×2), 129.0 (CH×2), 128.6, 128.5, 128.3,
127.1, 116.9 ppm; MS (ESI): m/z (%) = 258 (M++1, 100), 260 (M++3,
368).
2-(4-Fluorophenyl)-8-methyl-4H-benzo[d][1,3]oxazin-4-one (4l):
White solid; m.p. 195.3–196.1 °C; IR (KBr): νmax = 2925, 1776, 1621,
1592, 1508, 1460, 1413, 1312, 1234, 1155, 1055, 1004, 842, 767, 737
1
cm−1; H NMR (400 MHz, CDCl3): δ = 8.32 (dd, J1 = 5.6 Hz, J2 =
8.0 Hz, 2H, ArH), 8.06 (d, J = 7.6 Hz, 1H, ArH), 7.65 (d, J = 7.2 Hz,
1H, ArH), 7.38 (t, J = 7.2 Hz, 1H, ArH), 7.18 (t, J = 8.0 Hz, 2H, ArH),
2.64 (s, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ = 165.2 (d,
1JCF = 252 Hz), 159.6 (C=O), 154.7 (C=N), 144.9, 137.2, 135.9, 130.4
3
2
(d, JCF =9 Hz) (CH×2), 127.5, 126.6, 126.0, 116.5, 115.8 (d, JCF =
22 Hz) (CH×2), 17.2 (CH3) ppm; MS (ESI): m/z (%) = 256 (M++1,
100); HRMS-ESI: Calcd for C15H11FNO2 (M+1)+ 256.0774; found:
256.0763.
7-Chloro-2-(3-methoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one
(4m): White solid; m.p. 146.3–146.9 °C; IR (KBr): νmax = 2925, 1761,
1619, 1599, 1466, 1319, 1242, 1046, 1013, 874, 833, 775, 723 cm−1;
1H NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 8.4 Hz, 1H, ArH), 7.90
(d, J = 8.0 Hz, 1H, ArH), 7.81 (s, 1H, ArH), 7.71 (d, J = 1.6 Hz, 1H,
ArH), 7.48 (dd, J1 = 1.6 Hz, J2 = 8.4 Hz, 1H, ArH), 7.43 (t, J = 8.0 Hz,
1H, ArH), 7.15 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H, ArH), 3.93 (s, 3H,
OCH3) ppm; 13C NMR (100 MHz, CDCl3): δ = 159.7, 158.5 (C=O),
157.9 (C=N), 147.8, 142.8, 131.0, 129.74, 129.71, 128.7, 126.9,
120.9, 119.7, 115.3, 112.6, 55.6 (OCH3) ppm; MS (ESI): m/z (%) =
288 (M++1, 100), 290 (M++3, 45); HRMS-ESI: Calcd for C15H11ClNO3
(M+1)+ 288.0427; found: 288.0415.
2-(4-Fluorophenyl)-4H-benzo[d][1,3]oxazin-4-one (4g): White solid;
m.p. 174.8–175.3 °C (lit18 174–176 °C); IR (KBr): νmax = 3072, 1763,
1623, 1512, 1473, 1415, 1322, 1241, 1162, 1063, 1007, 843, 770 cm−1;
1H NMR (400 MHz, CDCl3): δ = 8.33 (dd, J1 = 5.2 Hz, J2 = 8.4 Hz,
2H, ArH), 8.24 (d, J = 8.0 Hz, 1H, ArH), 7.84 (t, J = 8.0 Hz, 1H, ArH),
7.69 (d, J = 8.0 Hz, 1H, ArH), 7.53 (t, J = 8.0 Hz, 1H, ArH), 7.20
(t, J = 8.4 Hz, 2H, ArH) ppm; 13C NMR (100 MHz, CDCl3): δ = 165.3
7-Chloro-2-(4-methoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one
(4n): White solid; m.p. 194.1–194.5 °C; IR (KBr): νmax = 2909, 1762,
1
(d, JCF = 252 Hz), 159.1 (C=O), 156.0 (C=N), 146.7, 136.5, 130.5

126 JOURNAL OF CHEMICAL RESEARCH 2012
1598, 1514, 1463, 1321, 1269, 1242, 1178, 1082, 1023, 836, 773 cm−1;
1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 9.2 Hz, 2H, ArH),
8.12 (d, J = 8.4 Hz, 1H, ArH), 7.64 (d, J = 2.0 Hz, 1H, ArH), 7.41 (dd,
J1 = 2 Hz, J2 = 8.4 Hz, 1H, ArH), 6.99 (d, J = 8.8 Hz, 2H, ArH), 3.90
(s, 3H, OCH3) ppm; 13C NMR (100 MHz, CDCl3): δ = 163.7, 159.1
(C=O), 158.4 (C=N), 148.6, 143.0, 130.7 (CH×2), 130.0, 128.4,
126.9, 122.3, 115.3, 114.5 (CH×2), 55.9 (OCH3) ppm; MS (ESI): m/z
(%) = 288 (M++1, 100), 290 (M++3, 35); HRMS-ESI: Calcd for
C15H11ClNO3 (M+1)+ 288.0427; found: 288.0417.
References
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P.W. Hsieh, H.P.Yu,Y.J. Chang and T.L. Hwang, Eur. J. Med. Chem., 2010,
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K.R. Shreder, J. Cajica, L. Du, A. Fraser, Y. Hu, Y. Kohno, E.C.K. Lin,
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7-Chloro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (4o): White solid;
5
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T. Teshima, J.C. Griffin and J.C. Powers, J. Biol. Chem., 1982, 257, 5085.
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m.p. 193.4–194.2 °C (lit20 192 °C); IR (KBr): νmax = 1756, 1613, 1596,
1
1561, 1463, 1315, 1237, 1062, 1022, 886, 833, 779 cm−1; H NMR
(400 MHz, CDCl3): δ = 8.32–8.29 (m, 2H, ArH), 8.17 (d, J = 8.4 Hz,
1H, ArH), 7.71 (d, J = 2.0 Hz, 1H, ArH), 7.63–7.58 (m, 1H, ArH),
7.55–7.51 (m, 2H, ArH), 7.48 (dd, J1 = 2.0 Hz, J2 = 8.4 Hz, 1H, ArH)
ppm; 13C NMR (100 MHz, CDCl3): δ = 158.9 (C=O), 158.4 (C=N),
148.2, 143.1, 133.2, 130.04, 129.99, 129.0 (CH×2), 128.9, 128.6
(CH×2), 127.2, 115.6 ppm; MS (ESI): m/z (%) =234 (100), 258
(M++1, 40), 260 (M++3, 13).
8
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We are grateful to the National Natural Science Foundation of
China (No. 200906083) and Natural Science Foundation of
Zhejiang Province (No. Y40900488) for financial support.
We also thank Prof. T. Zhou and Dr. Y. M. Ma for helpful
discussions.
Received 19 January 2012; accepted 31 January 2012
Paper 120118 doi: 10.3184/174751912X13285455672357
Published online: 22 March 2012
20 D.R. Desai, V.S. Patel and S.R. Patel, J. Indian Chem. Soc., 1966, 43, 351.

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