Synthesis of benz[d]oxazolones involving concomitant acetyl migration from oxygen to nitrogen

Article abstract of DOI:10.1080/00397910903245158

Heating of o-acetoxybenzoyl azides 6-10 in toluene leads to the Curtius reaction, which, when followed by closure of oxazolone ring with concomitant migration of acetyl group from oxygen to nitrogen, produces 3-acetoxybenz[d] oxazol-2(3H)-ones 11-15, which undergo hydrolysis with hot dilute hydrochloric acid to furnish benz[d]oxazol-2(3H)-ones 17-21. Thermal reaction of 2-hydroxy-5-nitrobenzoyl azide (22) in toluene finally yields a mixture of 5-nitrobenz[d]oxazol-2(3H)-one (20) and 5-nitrobenz[d]isoxazol-3(2H)-one (23). Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903245158

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Synthesis of Benz[d]oxazolones Involving
Concomitant Acetyl Migration from
Oxygen to Nitrogen
Sibdas Ray a & Sukla Ghosh b
a Department of Chemistry , University College of Science,
University of Calcutta , Kolkata, India
b Department of Chemistry , Gobardanga Hindu College , Khantura,
India
Published online: 26 Jul 2010.
To cite this article: Sibdas Ray & Sukla Ghosh (2010) Synthesis of Benz[d]oxazolones Involving
Concomitant Acetyl Migration from Oxygen to Nitrogen, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 40:16, 2377-2388, DOI:
10.1080/00397910903245158
To link to this article: http://dx.doi.org/10.1080/00397910903245158
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Synthetic Communications1, 40: 2377–2388, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903245158
SYNTHESIS OF BENZ[d]OXAZOLONES INVOLVING
CONCOMITANT ACETYL MIGRATION FROM OXYGEN
TO NITROGEN
Sibdas Ray1 and Sukla Ghosh2
1Department of Chemistry, University College of Science, University of
Calcutta, Kolkata, India
2Department of Chemistry, Gobardanga Hindu College, Khantura, India
Heating of o-acetoxybenzoyl azides 6–10 in toluene leads to the Curtius reaction, which,
when followed by closure of oxazolone ring with concomitant migration of acetyl group from
oxygen to nitrogen, produces 3-acetoxybenz[d]oxazol-2(3H)-ones 11–15, which undergo
hydrolysis with hot dilute hydrochloric acid to furnish benz[d]oxazol-2(3H)-ones 17–21.
Thermal reaction of 2-hydroxy-5-nitrobenzoyl azide (22) in toluene finally yields a mixture
of 5-nitrobenz[d]oxazol-2(3H)-one (20) and 5-nitrobenz[d]isoxazol-3(2H)-one (23).
Keywords: Benz[d]oxazolone; concomitant migration; 5-nitrobenz[d]isoxazolone; o-acetoxybenzoyl azides;
O to N acetyl migration
INTRODUCTION
Benzoxazoles, especially the benz[d]oxazolone compounds, are of interest as
established or potential anticonvulsants,[1,2] cardiotonics,[3] central nervous system
agents[4], b-3-adrenergic receptor antagonists,[5] antivirals,[6,7] analgesic and anti-
inflamatory agents,[8,9] antimicrobials,[9–13] fungicides,[13] and herbicides and plant-
growth regulators.[14] The literature is ambiguous in reporting the syntheses of
benz[d]oxazol-2(3H)-ones and benz[d]isoxazol-3(2H)-ones. In one report, o-hydroxy-
phenylhydroxamic acid reacted with thionyl chloride and pyridine to yield
benz[d]isoxazol-3-one, theorectically through the intermediate formation of a chlor-
amine compound,[15] and in a different report, 4-(2-hydroxyphenyl)-2,5-dioxa-3-
thiazoline-5-oxide, prepared from o-hydroxyphenylhydroxamic acid and thionyl
chloride, furnished benz[d]isoxazol-3-one when treated with triethylamine.[16] Kinstle
and Darlog reported in 1977[16b] that they produced a mixture of benzoxazolone and
benzisoxazolone from o-hydroxyphenylhydroxamic acid under similar reaction con-
ditions. In continuation of our ongoing studies[17] on benz[d]oxazolone compounds,
we report the synthesis of 3-acetylbenz[d]oxazol-2(3H)-ones by thermal conversion
of o-acetoxy-benzoyl azides, with concomitant migration of acetyl group from
Received May 26, 2009.
Address correspondence to Sibdas Ray, Department of Chemistry, University College of Science,
University of Calcutta, Kolkata, India. E-mail: sibdas2002@yahoo.co.in
2377

2378
S. RAY AND S. GHOSH
oxygen to nitrogen, and subsequent hydrolysis of them with hot aqueous
hydrochloric acid to benz[d]oxazole-2(3H)-ones.
RESULTS AND DISCUSSION
There is a report[18] of conversion of the azide of salicylic acid to
benz[d]isoxazol-3(2H)-one by heating in benzene. Since we observed that the exo-
thermic reaction always occurs with explosive violence when carried out on a gram
scale, we surmised that use of o-acetoxybenzoyl azides 6–10 as the starting materials
when the acetoxy oxygen should have diminished nucleophilicity would form the
initial intermediates, and these would be followed by smooth Curtius reaction and
subsequent formation of the oxazole ring with concomitant migration of acetyl moi-
ety from oxygen to nitrogen to produce 3-acetylbenz[d]oxazol-2(3H)-ones 11–15 in a
one-pot reaction (Scheme 1). o-Acetoxybenzoyl azides were prepared from the cor-
responding o-acetoxybenzoic acid compounds in one-pot reactions following the
procedure of Weinstock.[19]
Reaction of 2-acetoxybenzoic acids 1–5 with ethyl chloroformate in aqueous
acetone in the presence of triethyl amine at ꢀ5 ꢁC (bath temperature) followed by
treatment with sodium azide produced 2-acetoxybenzoyl azide compounds 6–10 in
very good yields (Scheme 1). The product, in each case, was extracted with ether,
and careful removal of ether at 10 ꢁC under reduced pressure furnished the title com-
pound, which can be stored under refrigeration without decomposition for only a few
days. Because of the inherent unstable nature of the acyl azides, crystallization and
elemental analyses of 6–10 were not attempted. The compounds have been character-
ized by spectroscopic means. Thus, 8 shows infrared (IR, KBr) absorptions at 2140
þ
1
ðS; ꢀN ꢂ NÞ, 1765 (s, ArC¼O str.), 1690 (s, CH3-C¼O) cmꢀ1; H NMR (CDCl3)
signals at d 9.11 (d, 1H, Jm 1.9 Hz, H-6), 7.70 (dd, 1H, Jo 8.6 Hz, Jm 2.0 Hz, H-4),
7.01 (d, 1H, Jo 8.6 Hz, H-3), 2.41 (s, 3H, CH3); and 13C NMR (CDCl3) signals at d
168.98 and 168.96 (both s, two C¼O), 149.99 (s, C-2), 137.81 (d, C-4), 134.28 (d,
C-6), 125.92 (d, C-3), 125.16 (s, C-5), 119.03 (s, C-1), 20.79 (q, CH3).
2-Acetoxybenzoyl azides 6–10 were taken in dry toluene and placed in a water
bath whose temperature was raised slowly. The reaction started when the
Scheme 1. Conversion of 2-acetoxybenzoic acids 1–5 to 2-acetoxybenzoyl azides 6–10.

SYNTHESIS OF BENZ[d]OXAZOLONES
2379
Scheme 2. Conversion of 2-acetoxybenzoyl azides 6–10 to 3-acetylbenz[d]oxazol-2(3H)-ones 11–15.
temperature was ꢃ50 ꢁC; effervescence continued, and the temperature was raised
very slowly until it reached 80 ꢁC (Scheme 2). Removal of solvent from the reaction
mixture followed by crystallization of the product from petrol (60–80 ꢁC) furnished
3-acetylbenz[d]oxazol-2(3H)-ones 11–15 (Table 1). The compounds have been
1
assigned structures 11–15 based on their IR, H NMR, and 13C NMR data. Thus,
the IR spectrum of 11 shows two strong absorptions at 1840 and 1800 cmꢀ1 assign-
able to symmetrical and unsymmetrical C¼O stretching and a strong absorption at
1725 cmꢀ1 assignable to CH3C¼O carbonyl stretching. A three-proton singlet in its
1H NMR (CDCl3) spectrum at d 2.75 confirmed the presence of a NCOCH3 moiety.
In its 13C NMR (CDCl3) spectrum, 11 displayed two diagnostic methine carbon
signals at relatively low d values of 109.72 and 115.82 assignable to C-7 and C-4
respectively and only one quaternary carbon at a high d value of 142.00 for C-7a;
apart from two quaternary carbon signals at d 169.36 and 151.38 corresponding
to –COCH3 and C-2, the remaining quaternary carbon signal at d 127.50 can be
assigned to C-3a, supporting the attachment of C-3a to NCOCH3 and the signal
at d 24.80 to methyl carbon.
A plausible route for thermal conversion of the 2-acetoxybenzoyl azides 6–10
to 3-acetylbenz[d]oxazoles is depicted in Scheme 3. Curtius reaction of the acyl azides
6–10 initially leads to the formation of 2-acetyloxyphenyl isocyanate compound 16,
which may at once undergo anchimeric assistance of the acetoxy-oxygen, whereby a
nucleophilic character is developed on the nitrogen center and as a result the acetyl
group migrates from oxygen to nitrogen.
Table 1. Thermal reaction of o-acetoxybenzoyl azide (6–10) in toluene (Scheme 1)
Substrate
R
Time (h)
Product
Mp (ꢁC)
Yield (%)
6
7
H
5-Cl
6
11
12
13
14
15
85–86
140
158
91
88
85
85
82
5.25
6
8
5-Br
5-NO2
6-Oac
9
10
6
6.5
166–8
194–196

2380
S. RAY AND S. GHOSH
Scheme 3. Plausible mechanism of change of 2-acetoxybenzoyl azides 6–10 to 3-acetylbenz[d]oxazol-
2(3H)-ones 11–15.
Hydrolysis of 11–15 by heating with 5% aqueous hydrochloric acid on a steam
bath for 8 h afforded benz[d]oxazol-2(3H)-ones 17–21 (Scheme 4, Table 2). Assignment
of the structures 17–21 for the products is established spectroscopically, for example,
17 was assigned by strong and broad absorption, centered at 3500cmꢀ1, for the N-H
stretching and a pair of sharp peaks at 1750 and 1790cmꢀ1 for the symmetrical and
unsymmetrical stretching of C(2)¼ O respectively in its IR spectrum; support for this
structure (17) also comes from the signals in the 13C NMR (CDCl3) spectrum
obtainable at d144.06 (s, C-7a), 129.43 (s, C-3a), 109.96 (d, C-7), and 110.17 (d,
C-4). The two methine signals of relatively low dC values (109.96 and 110.17) rule
out the alternative possibility of the product being benz[d]isoxazol-3(2H)-one.
Subsequently, we attempted to assess the effect of the NO2 group at C-5 of sali-
cylic acid on the course of reaction during heating 2-hydroxy-5-nitrobenzoyl azide
(22) because the 5-nitro substituent would decrease the migratory aptitude of the
2-hydroxyphenyl ring, possibly suppressing the Curtius-type rearrangement; at the
same time, the 5-NO2 group diminishes the nucleophilicity of the 2-OH group as
Scheme 4. Hydrolysis of 3-acetylbenz[d]oxazol-2(3H)-ones 11–15 to benz[d]oxazol-2(3H)-ones 17–21.

SYNTHESIS OF BENZ[d]OXAZOLONES
2381
Table 2. Hydrolysis of 3-acetylbenz[d]oxazol-2(3H)-one (6–10) with 5(N) aqueous
hydrochloric acid at 85 ꢁC for 6 h
Substrate
R
Product
Mp (ꢁC)
Yield (%)
11
12
13
14
15
H
5-Cl
17
18
19
20
21
141–142
193–194
212–213
230–231
286–290
49
76
91
80
65
5-Br
5-NO2
6-OH
well, particularly because NO2 and OH are in mutually complementary positions.
This electronic effect should therefore reduce the capacity of OH to lend anchimeric
assistance. 5-Nitrosalicylic acid was converted to 22 following Weinstock’s protocol.
Compound 22 was heated under reflux in dry toluene for 10 h. Subsequent removal
of the solvent under reduced pressure produced a mixture of 5-nitrobenz[d]isoxazol-
3(2H)-one (23) and 2-hydroxy-5-nitrophenyl isocyanate (24). 1H NMR and 13C
NMR spectra of this mixture were recorded before any attempt of chromatographic
separation. Subsequent column chromatography of this mixture over silica gel, with
the provision of removing the solvent from the eluents under reduced pressure at
25 ꢁC, led to the separation of two components, 5-nitrobenz[d]-isoxazol-3(2H)-one
(23) and 5-nitrobenz[d]oxazol-2(3H)-one (20), in an approximately 1:1 ratio. The
latter is produced as a silica-gel-mediated change of 2-hydroxy-5-nitrophenyl iso-
cyanate (24) at room temperature (Scheme 5). Compound 23, crystallized as 23–
C2H5OH, corresponded to the following 1H NMR (CDCl3) and 13C NMR (CDCl3)
assignments: dH 1.38 (t, 3H, J 7.2 Hz, CH3 of ethanol), 4.39 (q, 2H, J 7.2 Hz, CH2 of
ethanol), 6.96 (d, 1H, Jo 9.2 Hz, H-7), 8.20 (dd, 1H, Jo 9.2 Hz and Jm 2.9 Hz, H-6),
8.64 (d, 1H, Jm 2.9 Hz, H-4), 11.43 (s, 1H, -NH) and dC 168.78 and 166.18 (both s,
Scheme 5. Conversion of 5-nitrosalicylic acid to a mixture of 5-nitrobenz[d]isoxazol-3(2H)-one (23) and
5-nitrobenz[d]oxazol-2(3H)-one (20).

2382
S. RAY AND S. GHOSH
C-2 and C-7a), 139.99 (s, C-5), 130.17 (d, C-4), 126.34 (d, C-6), 118.39 (d, C-7),
112.31 (s, C-3a), 62.51 (t, CH2-OH), 13.91 (q, CH3 of ethanol).
In conclusion, we have successfully generated a protocol of converting
2-hydroxybenzoyl azides to 3-acetylbenz[d]oxazole-2(3H)-ones and their acid-
catalyzed hydrolysis to benz[d]oxazol-2(3H)-ones. In a variation, upon heating in
refluxing toluene, 2-hydroxy-5-nitrobenzoyl azide underwent a change to produce
a mixture of two products that, on chromatographic separation over silica gel, gave
5-nitrobenz[d]oxazole-2(3H)-one and 5-nitrobenz[c]isoxazole-3(2H)-one.
EXPERIMENTAL
The melting points are uncorrected. IR spectra were recorded as KBr pellets on
a Perkin-Elmer-782 spectrophotometer, and UV spectra of ethanolic solution of the
1
compounds were recorded on a Hitachi U-2000 spectrophotometer. The H NMR
spectra in CDCl3 (if not mentioned otherwise) were run on a Bruker AM-300L
instrument operating at 300 MHz with tetramethylsilane (TMS) as internal standard,
and the 13C NMR spectra were run in CDCl3(if not mentioned otherwise) on the
same instrument operating at 75 MHz. The degree of proton attachment of the car-
bons was verified using the distortionless enhancement by polarization transfer
(DEPT-135) sequence. Silica gel (60–120 mesh) was used for chromatographic puri-
fication and separation. The solvents used were dried and distilled before use. Light
petrol refers to one with a boiling range 60–80 ꢁC.
General Procedure for the Synthesis of 2-Acetoxybenzoyl Azide and
Its Derivatives (6–10)
A solution of triethyl amine (14 mL, 0.1 mol) in acetone (170 mL) was added
portionwise to a well-stirred solution of o-acetoxybenzoic acid compounds 1–5
(0.08 mol) in a mixture of acetone (50 mL) and water (15 mL) at ꢀ5 ꢁC (placed in
an ice–salt bath). The temperature of the reaction mixture was maintained at
ꢀ5 ꢁC, and a solution of ethyl chloroformate (0.08 mol) in acetone (17 mL) was
subsequently added to it dropwise during 10 min. Stirring was continued at that
temperature for an additional period of 30 min. Then, a cold solution of sodium azide
(10.15 g, 0.15 mol) in water (50 mL) was added dropwise during 30 min to the
well-stirred reaction mixture at ꢀ 5 ꢁC, and the mixture was then stirred while main-
taining the same temperature for an additional period of 1 h. The reaction mixture
was poured into ice water (500 mL), and the oil was extracted with ether (3 ꢄ 100 mL).
The combined ether extract was washed with water (2 ꢄ 15 mL) and dried over anhy-
drous sodium sulfate. The solvent was removed from the dried extract under reduced
pressure from an ice–salt bath at ꢀ 5 ꢁC, and the low-melting waxy residue as the
crude title compound was immediately dissolved in dry toluene (50 mL) for its
thermal conversion. The spectroscopic data, given here, were obtained using the waxy
solid without purification. No elemental analysis was attempted.
Data
2-Acetoxybenzoyl azide (6). Low-melting waxy compound (yield 60%); mp
1
65 ꢁC (dec); IR: n (cmꢀ1) 2180, 1780, 1700, 1500, 1385; H NMR: d 2.36 (s, 3H,

SYNTHESIS OF BENZ[d]OXAZOLONES
2383
-CH3), 7.13 (d, 1H, J 7.8 Hz, H-3), 7.31 (t, 1H, J 7.8 Hz, H-5), 7.62 (t, 1H, J 7.8 Hz,
H-4), 8.00 (d, 1H, J 7.8 Hz, H-6).
5-Chloro-2-acetoxybenzoyl azide (7). This semisolid mass could not be iso-
lated and characterized; rather, it was immediately taken in dry toluene to use in the
next step.
5-Bromo-2-acetoxybenzoyl azide (8). Fibrous, shining yellowish white
material (yield 79%); mp 167–170 ꢁC (dec); IR: n (cmꢀ1) 2140, 1765, 1690, 1593,
1472, 1227, 1169; 1H NMR: d 9.11 (d, 1H, Jm 1.9 Hz, H-6), 7.70 (dd, 1H,
Jo 8.6 Hz, Jm 2.0 Hz, H-4), 7.01 (d, 1H, Jo 8.6 Hz, H-3), 2.41 (s, 3H, CH3); 13C
NMR : dc 168.98 and 168.96 (both s, both C¼O), 149.99 (s, C-2), 137.81 (d, C-4),
134.28 (d, C-6), 125.92 (d, C-3), 125.16 (s, C-5), 119.03 (s, C-1), 20.79 (q, CH3).
5-Nitro-2-acetoxybenzoyl azide (9). Yellowish solid (yield 66%); mp
146–148 ꢁC(dec.); IR: n (cmꢀ1) 3103, 2150, 1821 and 1775, 1696, 1621, 1534, 1476,
1352, 1316, 1237, 1180; 1H NMR: d 8.64 (s, 1H, H-6), 8.24 (d, 1H, Jo 8.7 Hz,
H-4), 7.66 (d, 1H, J 8.7 Hz, H-3), 2.62 (s, 1H, CH3); 13C NMR (DMSO-d6): dc
169.66, (s, CH3C¼O), 146.33 (s, C-2), 140.68 (s, C-5), 128.42 (s, C-1), 121.68 (d,
C-6), 110.60 and 110.31 (both d, C-3, C-4), 24.51 (q, CH3).
2,4-Diacetoxybenzoyl azide (10). Oily residue; IR: n (cmꢀ1) 2137, 1804,
1737 and 1691.
General Procedure for the Synthesis of 3-Acetylbenz[d]oxazol-
2(3H)-ones (11–15)
A solution of crude o-acetoxybenzoyl azides 6–10 (0.05 mol) in dry toluene
(50 mL) was directly placed in a water bath whose temperature was increased slowly.
At ꢃ 50 ꢁC, the effervescence in dry toluene solution started. Effervescence was sus-
tained by gradually increasing the temperature of the water bath. It took ꢃ6 h for
completion of the reaction, indicated by cessation of effervescence in boiling water
(Table 1). Removal of the solvent from the reaction mixture under reduced pressure
produced a colorless solid, which was crystallized from the benzene–petrol mixture.
Data
3-Acetylbenz[d]oxazol-2(3H)-ones (11). Fluffy white crystals (yield 91%);
mp 85–86 ꢁC; IR: n (cmꢀ1) 3100, 3020, 1840 and 1800, 1725,1600, 1480, 1380,
1320; UV: kmax (logE) 274.5 (3.25) nm; 1H NMR: d 2.75 (s, 3H, CH3),
7.20–7.27(m, 3H, H-5, H-6 and H-7), 8.06 (m, 1H, H-4); 13C NMR: dc 24.80(q,
CH3), 109.72 (d, C-7), 115.82 (d, C-4), 126.54 and 125.20 (each d, C-5 and C-6),
127.50 (s, C-3a), 142.00 (s, C-7a), 151.38 (s, C-2), 169.36 (s, CH3C¼O); HRMS:
177.04265 (177.042575 for C9H7NO3); EI-MS (70 eV), m=z: 177 (Mþ., 10.4%), 135
(100%), 91 (7.8%), 79 (14.9%). Found: C, 60.95; H, 3.88; N, 8.01. C9H7NO3 requires
C, 61.02; H, 3.95; N, 7.91%.
5-Chloro-3-acetylbenz[d]oxazol-2(3H)-ones (12). Colorless crystalline
solid (yield 88%); mp 140 ꢁC; IR: n (cmꢀ1) 3118, 1831, 1727, 1478, 1380, 1306,

2384
S. RAY AND S. GHOSH
1
1249, 1150; H NMR: d 8.86 (d, 1H, Jm 2.1 Hz, H-4), 7.22 (dd, 1H, Jo 8.6 Hz,
Jm2.1 Hz, H-6), 7.12 (d, 1H, Jo 8.6 Hz, H-7), 2.72 (s, 1H, CH3); 13C NMR: dc
168.98, (s, CH3C¼O), 151.09 (s, C-2), 140.68 (s, C-7a), 130.41 (s, C-5), 128.42 (s,
C-3a), 125.26 (d, C-6), 116.39 (d, C-4), 110.55 (d, C-7), 24.52 (q, CH3); EI-MS
(70 eV), m=z: 211 (Mþ., 72.5%), 169 (100%), 113 (71%). Found: C, 51.31; H, 2.66;
N, 6.83. C9H6NO3Cl requires C, 51.06; H, 2.84; N, 6.62%.
5-Bromo-3-acetylbenz[d]oxazol-2(3H)-one (13). Shining white crystals
1
(yield 85%); mp 158 ꢁC; IR: n (cmꢀ1) 3112, 1822, 1725, 1473, 1304, 1248, 1028; H
NMR: d 8.22 (d, 1H, Jm 2.0 Hz, H-4), 7.38 (dd, 1H, Jo 8.6 Hz, Jm 2.0 Hz, H-6),
7.08 (d, 1H, Jo 8.6 Hz, H-7), 2.57 (s, 1H, CH3); 13CNMR : dc 169.02, (s, CH3C¼O),
150.98 (s, C-2), 141.19 (s, C-7a), 128.72 (s, C-3a), 128.25 (d, C-6), 119.14 (d, C-4),
117.51 (s, C-5), 111.07 (d, C-7), 24.54 (q, CH3); HRMS: 254.95261 (254.95308 for
C9H6NO3Br); EI-MS (70 eV), m=z: 255 and 257 (Mþ. 12.3% and 11.9% respectively),
213 and 215 (100% and 97.7% respectively), 157 and 159 (9.3% and 8.9%). Found: C,
42.40; H, 2.49; N, 5.30. C9H6NO3Br requires C, 42.19; H, 2.34; N, 5.47%.
5-Nitro-3-acetylbenz[d]oxazol-2(3H)-one (14). Yellow crystalline solid
(yield 85%); mp 166–168 ꢁC (aqueous ethanol); IR: n (cmꢀ1) 3142, 1820, 1731,
1
1607, 1539, 1476, 1377, 1339, 1267, 1214, 1156; H NMR (DMSO-d6): d 8.60 (d,
1H, Jm 2.3 Hz, H-4), 8.24 (dd, 1H, Jo 8.9 Hz, Jm 2.3 Hz, H-6), 7.66 (d, 1H, Jo
8.9 Hz, H-7), 2.61 (s, 3H, CH3); 13C NMR (DMSO-d6): dc 169.77 (s, CH3C¼O),
150.77 (s, C-2), 146.34 (s, C-7a), 144.16 (s, C-5), 128.52 (s, C-3a), 121.69 (d, C-6),
110.61 and 110.31 (both d, C-4 and C-7), 24.52 (q, CH3); HRMS: 222.02754
(222.02764 for C9H6N2O5); EI-MS (70 eV), m=z: 222 (Mþ. 26.4%), 180 (100%),
164 (7.7%), 150 (15.4%), 134 (14.8%). Found: C, 48.53; H, 2.52; N, 12.80.
C9H6N2O5 requires C, 48.65; H, 2.70; N, 12.61%.
6-Acetoxy-3-acetylbenz[d]oxazol-2(3H)-one (15). Greyish white solid
(yield 82%); mp 194–196 ꢁC (chloroform-petrol); IR: n (cmꢀ1) 3027, 1644, 1440,
1
1331, 1240, 1153, 1093; H NMR (DMSO-d6): d 7.99 (d, 1H, Jo8.6 Hz, H-4), 7.31
(d, 1H, Jm 2.2 Hz, H-7), 7.01 (dd, 1H, Jo 8.6 Hz, Jm 2.2 Hz, H-5), 2.57 (s, 3H,
NCOCH3), 2.29 (s, 3H, CH3COO); 13C NMR (DMSO-d6): dc 169.52 and 169.15
(both s, two CH3CO), 151.16 (s, C-2), 147.44 (s, C-7a), 142.02 (s, C-6), 125.62 (s,
C-3a), 117.80 (d, C-4), 115.36 (d, C-5), 104.96 (d, C-7), 24.00 (q, CH3CON), 20.81
(q, CH3COO). Elemental analysis was not attempted due to failure to prepare a
sample of analytical purity.
General Procedure for the Synthesis of Benz[d]oxazol-2(3H)-ones
(17–21)
A suspension of 3-acetylbenz[d]oxazol-2-ones (6–10) (0.04 mol) in 5% aqueous
hydrochloric acid (250 mL) was stirred at ꢃ90 ꢁC for 8 h. On cooling, white solid
precipitated out and was collected by filtration. The solid was washed with cold
2% aqueous sodium bicarbonate solution (2 ꢄ 15 mL) followed by cold water
(2 ꢄ 10 mL) and recrystallized.

SYNTHESIS OF BENZ[d]OXAZOLONES
2385
Data
Benz[d]oxazol-2(3H)-one (17). Colorless shining crystals (yield 49%); mp
141–142 ꢁC[20,21] (lit. mp 138 ꢁC and 143–145 ꢁC respectively, chloroform-petrol);
IR: n (cmꢀ1) 3500, 3300–3200, 1790, 1750, 1500, 1415, 1325, 1270, 1160; UV:
k
max(logE) 274.0 (3.25), 225.5(3.49) nm; kmin (logE) 242.0 (2.66), 217.5(3.41) nm;
1H NMR: d 6.03 (br. s, 1H, N-H), 7.10–7.26 (m, 4H, aromatic protons); 13C
NMR: dc 155.80 (s, C-2), 144.06 (s, C-7a), 129.43 (s, C-3a), 124.11 and 122.76 (each
d, C-5 and C-6), 110.17 (d, C-4), 109.96 (d, C-7); EI-MS (70 eV), m=z: 135 (Mþ.,
100%), 91 (59%), 79 (80.5%). Found: C, 62.10; H, 3.81; N, 10.15. C7H5NO2 requires
C, 62.22; H, 3.70; N, 10.37%.
5-Chlorobenz[d]oxazol-2(3H)-one (18). Shining white crystals (yield 76%);
mp 193–194 ꢁC[21,22](lit. mp 190–191 ꢁC and 186–188 ꢁC respectively, ethanol); IR:
1
n (cmꢀ1) 3450, 3157, 1773, 1615, 1300, 1147; H NMR: d 11.76 (br. s, 1H, N-H),
7.21(dd, 1H, Jo 8.3 Hz, Jm 3.1 Hz H-6), 7.02–7.06 (m, 2H, H-4 and H-7); 13C
NMR: dc 154.30, (s, C-2), 142.21 (s, C-7a), 131.78 (s, C-5), 127.87 (s, C-3a),
121.51 (d, C-6), 110.72 (d, C-4), 109.84 (d, C-7); EI-MS (70 eV), m=z: 169 (Mþ.,
100%), 113 (71.8%), 78 (90.6%). Found: C, 49.65; H, 2.24; N, 8.46. C7H4NO2Cl
requires C, 49.56; H, 2.36; N, 8.26%.
5-Bromobenz[d]oxazol-2(3H)-one (19). Shining white crystals (yield 91%);
mp 212–213 ꢁC[23] (lit. mp 218–220 ꢁC, ethanol); IR: n (cmꢀ1) 3156, 3054, 1772,
1
1612, 1473, 1295, 1254, 1149; H NMR : d 7.97 (d, 1H, J 2.1 Hz, H-4), 7.45 (dd,
1H, Jo 8.5 Hz, Jm 2.1 Hz, H-6), 7.36 (d, 1H, Jo 8.5 Hz, H-7); 13C NMR (DMSO-d6):
dc 154.15, (s, C-2), 142.65 (s, C-7a), 132.12 (s, C-3a), 115.41 (s, C-5), 124.45 (d, C-6),
111.60 and 111.32 (both d, C-4 and C-7); EI-MS (70 eV), m=z: 213 and 215
(Mþ.,100%), 157 and 159 (69.6% and 70.8% respectively). Found: C, 39.04; H,
2.04; N, 6.22. C7H4NO2Br requires C, 39.25; H, 1.87; N, 6.54%.
5-Nitrobenz[d]oxazol-2(3H)-one (20). Yellow solid (yield 80%); mp
230–231 ꢁC[22,24] (lit. mp 228–230 ꢁC and 239–240 ꢁC, ethanol); IR: n (cmꢀ1
)
3080–3210, 1772.0, 1629.4, 1523.5, 1473.9, 1396.9, 1346.7, 1265.8, 1150.7, 1067.8;
1H NMR: d 7.93 (dd, 1H, Jo 8.9 Hz and Jm 2.4 Hz, H-6), 7.73 (d, 1H, Jm 2.4 Hz,
H-4), 7.40 (d, 1H, Jo 8.9 Hz, H-7); 13C NMR: dc 153.97 (s, C-2), 147.81 (s, C-5),
143.94 (s, C-7a), 131.21 (s, C-3a), 118.48 (d, C-6), 109.67 (d, C-4), 104.98 (d, C-7).
Found: C, 46.42; H, 2.43; N, 15.34. C7H4N2O4 requires C, 46.67; H, 2.22; N, 15.56%.
6-Hydroxybenz[d]oxazol-2(3H)-one (21). Greyish white solid (yield 65%);
mp 286–290 ꢁC[20] (lit. mp 265 ꢁC, ethanol); IR: n (cmꢀ1) 3348 and 3217, 1737,
1
1640, 1553, 1497, 1405, 1328, 1234, 1107; H NMR (DMSO-d6): d 11.26 (br. s,
1H, OH), 9.38 (br. s, 1H, NH), 6.82 (d, 1H, Jo8.2 Hz, H-4), 6.66 (d, 1H, Jm
2.1 Hz, H-7), 6.51 (dd, 1H, Jo 8.3 and Jm 2.1 Hz, H-5); 13C NMR (DMSO-d6): dc
154.89 and 153.14, (both s, C-2 and C-6), 144.14 (s, C-7a), 122.37 (s, C-3a),
110.90 and 109.90 (both d, C-4 and C-5), 99.06 (s, C-7). Found: C, 55.42; H, 3.51;
N, 9.06. C7H5NO3 requires C, 55.63; H, 3.31; N, 9.27%.

2386
S. RAY AND S. GHOSH
Synthesis of 2-Hydroxy-5-nitrobenzoyl Azide (22)
This was achieved starting from 5-nitrosalicylic acid and following the general
procedure for the synthesis of 2-acetoxybenzoyl azide and its derivatives; it was crystal-
lized as 22–C2H5OH (yield 23%); mp 280–281 ꢁC; IR: n (cmꢀ1) 3400, 3080, 2160, 1700,
1615, 1560, 1510, 1485, 1450, 1350, 1325, 1310, 1260, 1230; 1H NMR: d 1.44 (t, 3H, J
7.0 Hz, CH3 of ethanol), 4.99 (q, 2H, J 7.0 Hz, CH2OH), 7.08 (d, 1H, Jo 9.2 Hz, H-3),
8.33 (dd, 1H, Jo 9.2 Hz, Jm 2.8 Hz, H-4), 8.79 (d, 1H, Jm 2.8 Hz, H-6), 11.45 (s, OH).
Synthesis of 5-Nitrobenz[d]oxazol-2(3H)-one (20) and
5-Nitro-benz[d]isoxazol-3(2H)-one (23) from 22
The crude yellow material of 2-hydroxy-5-nitrobenzoyl azide (22) (2.0 g,
0.009 mol) was heated in toluene (50 mL) under reflux for 10 h. The solvent was
removed from the reaction mixture at 25 ꢁC under reduced pressure to get an yellow
solid as a mixture of two products, 23 and 5-nitro-2-hydroxyphenyl isocyanate (24);
its IR spectrum (as KBr pellet) showed absorptions at 3350–3380 (br.), 2160, and
1
1680–1710 cmꢀ1. H NMR spectrum analyses for two sets of protons corresponded
to two compounds in a ꢃ 1:1 ratio.
Set I: d 8.51 (d, Jm 3.6 Hz), 7.76 (dd, J0 9.0 Hz, Jm 2.8 Hz), and 6.89 (d, J0
9.0 Hz) for the protons attached to C-4, C-6, and C-7 respectively of 5-nitrobenz[d]i-
soxazol-3(2H)-one (23).
Set II: d 7.44 (s), 7.55 (distorted d) and 6.16 (d, J0 9.0 Hz) corresponded to
5-nitro-2-hydroxyphenyl isocyanate (24).
This mixture of products was separated by column chromatography on silica
gel using 20% methanolic chloroform for elution. Two products, 5-nitrobenz[d]oxa-
zol-2(3H)-one (20) and 5-nitrobenz[d]isoxazol-3(2H)-one (23), were obtained in an
almost 1:1 ratio; 20 was obtained first, followed by 23.
5-Nitrobenz[d]oxazol-2(3H)-one (20). Mp 230–234 ꢁC, IR spectrum super-
1
imposable with that of 20 prepared from hydrolysis of 14; H NMR: d 7.40 (d,
1H, J0 8.9 Hz, H-7), 7.73 (d, 1H, Jm 2.4 Hz, H-4), 7.93 (dd, 1H, Jo 8.9 Hz and Jm
2.4 Hz, H-6). 13C NMR: dc 153.98 (s, C-2), 147.81 (s, C-5), 143.94 (s, C-7a),
131.21 (s, C-3a), 118.48 (d, C-6), 109.67 (d, C-4), 104.98 (d, C-7).
5-Nitrobenz[d]isoxazol-3(2H)-one (23). Compound 23 crystallized as
1
23–C2H5OH, mp 206–207 ꢁC[25] (lit. mp 205–207 ꢁC); H NMR: d 1.38 (t, 3H, J
7.2 Hz, CH3 of ethanol), 4.39 (q, 2H, J 7.2 Hz, -CH2 of ethanol), 6.96 (d, 1H, Jo
9.2 Hz, H-7), 8.20 (dd, 1H, Jo 9.2 Hz and Jm 2.9 Hz, H-6), 8.64 (d, 1H, Jm 2.9 Hz,
H-4), 11.43 (1H, s, NH). 13C NMR: dc 168.78 and 166.18 (both s, C-2 and C-7a),
139.99 (s, C-5), 130.17 (d, C-4), 126.34 (d, C-6), 118.39 (d, C-7), 112.31 (s, C-3a),
62.51 (t, CH2-OH), 13.91 (q, CH3 of ethanol).
ACKNOWLEDGMENTS
1
We thank A. Acharya and P. Ghosh for H NMR and 13C NMR spectral
measurements. One of the authors (S. G.) is thankful to the University Grants
Commission, New Delhi, and the Council for Scientific and Industrial Research,
New Delhi, for a research fellowship.

SYNTHESIS OF BENZ[d]OXAZOLONES
2387
REFERENCES
1. Ucar, H.; Derpoorten, K. V.; Cacciaguerra, S.; Spampinato, S.; Stables, J. P. Synthesis
and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone deriva-
tives. J. Med. Chem. 1998, 41, 1138–1145.
2. Upasani, R.; Cai, S. X.; Lan, N. C.; Wang, Y.; Field, G.; Fick, D. B. Preparation of sub-
stituted quinoxazolines and heterocyclic analogues as antagonists of positive modulators
of AMPA receptor. Patent WO 9944612, 1999; Chem. Abstr. 1999, 131, 214294.
3. Okujima, H.; Narimatsu, A.; Furuya, R.; Kitada, Y. (Heterocyclylamino)-2(3H)-
benzoxazolones as their salts as cardiotonics. JP 02059575, 1990; Chem. Abstr. 1990,
113, 59162.
4. Verma, R. S.; Chauhan, S. M.; Prasad, C. R. Synthesis of substituted 2-phenylbenzoxa-
zoles as CNS active agents. Indian J. Chem. 1985, 24B, 280.
5. Delhomel, J. F.; Yous, S.; Depreux, P.; Lesieur, D. Synthesis of 2(3H)-benzoxazolone and
2(3H)-benzothiazolone derivatives as potential b-3-adrenergic receptor. J. Heterocycl.
Chem. 2001, 38, 633–639.
6. Misra, V. S.; Sen, S.; Srivastava, N.; Verma, H. N.; Khan, M. M. A. A.; Khan, S. K. Syn-
thesis of new 4-arylazo-1-(5-substitutedbenzoxazolin-20-oxy-acetyl)-3-methylpyrazolin-5-
ones and their evaluation as antiviral agents. Ind. J. Pharm. Sc. 1987, 49, 40–42, 47; Chem.
Abstr. 1988, 109, 170314.
7. Neikova, N.; Simov, D.; Galunska, G.; Velichkova, E.; Galabov, A. S.; Karparov, A.
Benzoxazolone-5-sulfonamides, 1-(benzoxazolone-50-sulfonyl)-benzotriazoles, and 4-
hydroxy-3,20-diaminobenzenesulfonamides with antiviral activity. Arzneim. Forsch.
1981, 31, 747–752.
8. Erol, D. D.; Sunal, R.; Duru, S. Synthesis and screening of analgesic and anti-
inflammatory activity of 6-aryl-3-(4-substitutedbenzoylmethyl)-2(3H)-benzoxazolones.
Arzneim. Forsch. 1990, 40, 478–480.
9. Erdogan, H.; Debaert, M.; Cazin, J. C. Synthesis of some 2-benzoxazolinone derivatives
and their analgesic properties. Arzneim. Forsch. 1991, 41, 73–76.
10. Erol, D. D.; Aytemir, M. D.; Yulug, N. Synthesis and antimicrobial activity of
thiazolinomethyl-2(3H)-benzoxazolone derivatives, I. Eur. J. Med. Chem. 1995, 30,
521–524.
11. Kalcheva, V.; Mincheva, Z.; Andreva, P. Synthesis and in vitro activity of new cephalos-
porin derivatives containing a benzoxazolone ring. Arzneim. Forsch. 1990, 40, 1030–1034.
12. Erol, D. D.; Rosen, A.; Erdogan, H.; Yulug, N. Synthesis of some new Mannich bases
derived from 6-acyl-3-(3,5-dimethylpiperidinomethyl-2(3H)-benzoxazolones and their
biological activities. Arzneim. Forsch. 1989, 39, 851–853.
13. Erol, D. D.; Aytemir, M. D.; Yulug, N. Synthesis and antibacterial and antifungal proper-
ties of thiazolinoethyl-2(3H)-benzoxazolone derivatives, II. Eur. J. Med. Chem. 1996, 31,
731–734.
14. Kalcheva, V.; Khadzhieva, B.; Gulubov, B. Synthesis of 1-(2-hydroxyaryl) and 1-methyl-
1-(2-hydroxy)-3-n-butyl urea. Izvestiya po Khimiya, 1988, 21, 101–105; Chem. Abstr. 1989,
110, 38704.
15. Meisenheimer, J.; Senn, O.; Zimmermann, P. Oximes of an o-aminobenzo and aceto-
phenone. Ber. Deut. Chem. Ges 1927, 60, 1736–1748.
16. (a) Boeshagen, H. 3-Hydroxy-1,2-benzisoxazoles. Ger. Patent 1,157,231, 1961; Chem.
Abstr. 1964, 60, 30963; (b) Kinstle, T. H.; Darlage, L. J. Thermal conversion of
3-hydroxy-1,2-benzoxazole to benzoxazolinone. J. Heterocycl. Chem. 1969, 6, 123–124.
17. Ray, S.; Ghosh, S.; Ganguly, N. C. Novel sulfur-to-nitrogen migration of ethenylmethyl
moiety in benz[d]oxazole system via internal radical capture. Synth. Commun. 2006, 36,
1447–1457.

2388
S. RAY AND S. GHOSH
18. Lindemann, H.; Schuttheis, W. 2-Hydroxyinoxazine. Ann. Chem. J. Liebig 1927, 451,
241–255.
19. Weinstock, T. A modified Curtius reaction. J. Org. Chem. 1961, 26, 3511.
20. Cole, E. R.; Crank, G. S. Oxidation with lead tetraacetate, VI: Oxidation of benzimida-
zoles, benzoxazoles, and benzthiazoles. Aust. J. Chem. 1986, 39, 295–301.
21. Takeda, K.; Ogura, H. Studies on heterocyclic compounds, XLIII: Insertion reaction of
carbonyl group using disuccinimido carbonate (DSC). Synth. Commun. 1982, 12, 213–217.
22. Kim, S.; Ko, Y. K. Preparation of cyclic carbonates and 2-oxazolidones using di-2-pyridyl
carbonates. Heterocycles 1986, 24, 1625–1630.
23. Sam, J.; Richmond, C. W.; Valentine, J. L. 3-Aminoalkyl-2-benzoxazo-linones. J. Med.
Chem. 1967, 10, 408–410.
24. Miyata, T.; Kanabe, N.; Murai, S.; Sonoda, N.; Nishiguchi, I.; Hirashima, T. A new
synthesis of benzimidazolones, benzoxazolones, and benzothiazolones from o-substituted
nitrobenzenes using sulfur and carbonmonoxide. Nippon Kagaku Kaishi. 1987, 1332–1337;
Chem. Abstr. 1987, 108, 94463.
25. Wrubel, J. 2-Substituted-5-amino-1,2-benzisoxazoles. Z. Chem. 1980, 20, 18.