Synthesis of 2-oxo-[1,2,4]triazolo[3,2-d] [1,5]benzoxazepines: A kind of novel tricyclic O,N-heterocycles

Article abstract of DOI:10.1081/SCC-120030757

The synthesis of a series of novel tricyclic O,N-heterocycles 7a-k, a kind of unprecedented 2-oxo-[1,2,4]triazolo[3,2-d][1,5]benzoxazepine derivatives, has been accomplished, featuring acid-induced ring closure of the geminal arylazo isocyanato compounds 5, which were prepared from chroman-4-ones in three steps, followed by feasible ring expansion and basic work-up.

Full text of DOI:10.1081/SCC-120030757

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Synthesis of 2‐Oxo‐[1,2,4]triazolo[3,2‐d]
[1,5]benzoxazepines: A Kind of Novel Tricyclic
O,N‐Heterocycles
Zheng Li a , Quanrui Wang a & Fenggang Tao a
a Department of Chemistry , Fudan University , Shanghai, 200433, China
Published online: 16 Aug 2006.
To cite this article: Zheng Li , Quanrui Wang & Fenggang Tao (2004) Synthesis of 2‐Oxo‐[1,2,4]triazolo[3,2‐d]
[1,5]benzoxazepines: A Kind of Novel Tricyclic O,N‐Heterocycles, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 34:9, 1691-1702, DOI: 10.1081/SCC-120030757
To link to this article: http://dx.doi.org/10.1081/SCC-120030757
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 9, pp. 1691–1702, 2004
Synthesis of 2-Oxo-[1,2,4]triazolo[3,2-d]
[1,5]benzoxazepines: A Kind of Novel
Tricyclic O,N-Heterocycles
*
Zheng Li, Quanrui Wang, and Fenggang Tao
Department of Chemistry, Fudan University,
Shanghai, China
ABSTRACT
The synthesis of a series of novel tricyclic O,N-heterocycles 7a–k, a kind
of unprecedented 2-oxo-[1,2,4]triazolo[3,2-d][1,5]benzoxazepine deriva-
tives, has been accomplished, featuring acid-induced ring closure of the
geminal arylazo isocyanato compounds 5, which were prepared from
chroman-4-ones in three steps, followed by feasible ring expansion and
basic work-up.
Key Words: O,N-Heterocycles; Synthesis; Chroman-4-ones; Column
chromatography; Ring expansion.
*
Correspondence: Quanrui Wang, Department of Chemistry, Fudan University, Shanghai
200433, China; Fax: þþ86-2165641740; E-mail: qrwangb@online.sh.cn.
1691
DOI: 10.1081/SCC-120030757
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Li, Wang, and Tao
INTRODUCTION
Many [1,2,4]triazolobenzoheteroazepine derivatives show important
biological activities.[1–4]They have been used as drugs or candidates as anti-
psychotic agents, as carrageenin-induced edema inhibitors, for inhibiting
phospholipase A2, and also for treatment of osteoporosis. The attachment of
a triazolo ring to the heptatomic ring provides the potentiality to enhance
the pharmacological activity and/or offer more interesting properties.[5,6] It
is not surprising, therefore, that there has been a significant and ever increas-
ing interest in the design and synthesis of this class of heterocyles.[7,8]
We have previously established an efficient synthetic pathway to obtain
[1,2,4]triazolo[3,2-d][1,5]benzoxazepines and their chalcogen analogs start-
ing from chroman-4-ones and thiochroman-4-ones, respectively.[9] We have
also successfully expanded the reaction sequence to the synthesis of novel
thieno[2,3-f][1,2,4]triazolo[1,5-a]azepines by starting from 6,7-dihydrobenzo
[b]thiophen-4(5H)-one.[10]
On the other hand, during the course of investigation on rearrangement of
various 3,3-disubstituted-1-aryl-4,5-dihydro-5-oxo-3H-1,2,4-triazolium salts,
Gstach et al. originally established an efficient entry to 1,5-annulated 1,2-
dihydro-2-aryl-3H-1,2,4-triazol-3-ones.[11] Except the particular interests in
the theoretical aspects,[12] such as the high selectivity and the nature of the
transition states for migration, the method seems to be valuable to synthesize
2-aryl substituted 1,2-dihydro-1,2,4-triazol-3-ones 1.
Our continued interest in the synthesis of tricyclic compounds spurred us
to test the potentiality to the synthesis of novel 1,2,4-triazolo fused benzox-
azepine ring systems. We now show that a kind of novel 2-oxo-[1,2,4]-
triazolo[3,2-d][1,5]benzoxazepines can be furnished by employment of
chroman-4-ones that are readily accessible from substituted phenols.
The approach reported in this paper is illustrated in Sch. 1. The required
chroman-4-ones 2 were readily attainable according to literature via the initial
Michael-type addition of the respective aryloxide ion to the double bond of
acrylonitrile followed by acid-catalyzed hydrolysis of the nitrile group to
carboxylic acid and final intramolecular ring closure.[13] Condensation of
ketones 2a–e with an appropriate arylhydrazine in refluxing ethanol contain-
ing a catalytic amount of acetic acid furnished the arylhydrazones 3a–k in

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1693
Scheme 1.
nearly quantitative yield, which were sufficiently pure (1H NMR) and applied
for the next reaction as obtained.
Phenylhydrazone of chroman-4-one (3a) was allowed to react with a
5-fold excess of potassium isocyanate in acetic acid leading to the 5-spiro
substituted 1-aryl-1,2,4-triazolidin-3-one 4a in 63% yield. The reaction fea-
tures a 1,3-dipolar cycloaddition with the hydrazone moiety as the 1,3-dipole

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Li, Wang, and Tao
and isocyanic acid (generated in situ) as the dipolarophile. Since the 1,3-dipo-
lar cycloaddition steps 3 ! 4 are seemingly crucial ones in our overall syn-
thetic sequences, the scope of the reaction was investigated using different
arylhydrazones. We found that 4-chlorophenyl hydrazones and 4-bromophe-
nyl hydrazones worked pleasingly equally well. However, attempts to trans-
form the arylhydrazones 3 in which aryls are more electron attracting (e.g.,
Ar ¼ 4-NO2C6H4 and C6F5) into the corresponding 5-spiro substituted
1-aryl-1,2,4-triazolidin-3-ones 4 were unsuccessful, even under more harsh
conditions (elevated reaction temperature, prolonged reaction time and appli-
cation of more quantities of potassium cyanate). This is in contrast to arylhy-
drazones of simple aliphatic ketones, which show higher tolerances to the aryl
substituent.[11a]
Oxidative ring cleavage of 4a was carried out using 1.2 equiv. of potass-
ium permanganate in a two-phase system (H2O/1 : 1 mixture of Et2O and
CH2Cl2) providing the bicyclic geminal arylazo isocyanate 5a in 92% yield.
Similarly, other 5-spiro substituted 2-aryl-1,2,4-triazolidin-3-ones 4b–k
were converted to the respective 1-isocyanto-1-(arylazo)cycloalkanes 5b–k
in high yields. The presence of an isocyanato group in 5 was substantiated
by sharp IR absorption at about 2200 cm21
.
Upon addition of a 50% aqueous solution of tetrafluoroboric acid to a
cooled (08C) solution of the isocyanates 5 in Et2O, highly reactive intermedi-
ates 3-spiro substituted 4,5-dihydro-5-oxo-1-aryl-3H-1,2,4-triazolium tetra-
fluoroborates 6 were formed. Under mild conditions, 6 underwent quick
rearrangement with concurrent ring expansion and insertion of the nitrogen
atom into the carbon skeleton to yield the salts of 1,5-annulated 1,2-di-
hydro-2-aryl-3H-1,2,4-triazol-3-ones 7a–k in less than 5 min. The neutral
free tricyclic heterocycles 7a–k have been prepared after basic work-up. In
all instances, the ring expansion of the benzannulated 6 occurs exclusively
with migration of the aromatic side of the ring (Sch. 1, route i), yielding 7
as the sole products. The stereoisomers 8 which would have formed by
migration of the aliphatic side (Sch. 2, route ii) are not observed. This is
just what we expected on the basis of our closely related reaction.[9,10] It
should be noted, however, that the study on the rearrangement of the open
chain analogs, i.e., 3-alkyl-4,5-dihydro-5-oxo-1,3-diphehyl-3H-1,2,4-triazo-
lium tetrafluoroborates, has made the following migratory order: Et . Ph
and Ph . Me.[11a] Although the nature of the migration as well as the precise
factors that govern the migratory aptitude are not completely clear, known
facts and theoretical studies suggest that the electronic character of the substi-
tuents contributes principally and the relative migratory aptitude seems to
parallel their ability to stabilize the respective carbocation despite of the
electron deficiency at the migrating terminus.[12a] But, in our cases, both steric
and conformational factors also surely come into play.

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Novel Tricyclic O,N-Heterocycles
1695
Scheme 2.
The products 7 were identified from spectroscopic data. To provide
undoubted structural proof, the x-ray diffraction analysisa was carried out
for 7a. A perspective drawing of the molecule of 7a is shown in Fig. 1.
In summary, we reported, herein, the synthesis of 2-oxo-[1,2,4]tria-
zolo[3,2-d][1,5]benzoxazepines, which represent a kind of novel tricyclic
heterocycles, 1,5-annulated 1,2-dihydro-2-aryl-3H-1,2,4-triazol-3-ones under
ambient conditions. Incorporation of a triazolo ring onto the seven-membered
ring and the obvious structural relationship to literature precedents render these
novel tricyclic heterocycles to be of considerable potential pharmaceutical
interests.
EXPERIMENTAL
Melting points are uncorrected. IR spectra were recorded on a Mattson
Alpha-centauri FT-IR spectrometer. NMR spectra were acquired on a Brucker
aCrystal data for 7a. C16H13N3O2, M ¼ 279.30, a ¼ 8.929(3), b ¼ 18.817(7),
3
˚
˚
c ¼ 7.923(3) A, U ¼ 1331.2(8) A , space group Pna21, Z ¼ 4, T ¼ 298(2)K,
rcalc ¼ 1.394 g cm23, m ¼ 0.09 mm21, 6249 reflections were measured, 2562 unique
which were used in all least square calculations, R1(F) ¼ 0.0220 (for 238 reflections
with F20 ꢀ 2s(F02), vR2(F2) ¼ 0.0869 for all unique reflections.

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Li, Wang, and Tao
Figure 1. View of the molecule 7a with the atom-labeling scheme.
AMX 500 spectrometer at 500 MHz (1H NMR) and 125 MHz (13C NMR),
respectively, in the solvents indicated. Chemical shifts (d) are reported in
parts per million (ppm) relative to Me4Si. Coupling constants (J) are given
in Hertz (Hz). Mass spectra and high-resolution mass spectra were performed
on a Varian MAT 44S with EI ionization. Analytical TLC was performed on
silica gel nonactivated plates.
2-Arylspiro[1,2,4-triazolidine-5,40-chroman]-3-ones 4a–k:
General Procedure
Arylhydrazine (20 mmol) was added to a solution of the appropriate
chroman-4-one (20 mmol) 2 in EtOH (30 mL). The mixture containing a catalytic
amount of AcOH (ꢀ0.5 mL) was heated under reflux for 1–3 hr (monitored by
TLC, EtOAc/P.E. (60–908C), 1 : 5). Reduced pressure rotary evaporation at
308C gave the corresponding chroman-4-one arylhydrazone 3 as pure product
(1H NMR) and was employed as the substrate without further purification.
To a 458C stirred mixture (solution or suspension) of the hydrazone 3 in
glacial acetic acid (40 mL) and water (3 mL) solid potassium cyanate (9.73 g,
120 mmol) was added in 1 g portions within 5 hr. The mixture was stirred for
an additional 90 min at r.t. until the crystallization process was initiated. Upon
careful addition of ice-cold water (50 mL) precipitation of the crude product
was completed, which was filtered, washed with water until neutral, and
dried in vacuo (P2O5). The unreacted hydrazone was removed by refluxing
a suspension of the crude product in Et2O (20 mL) for 10 min. The desired

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Novel Tricyclic O,N-Heterocycles
1697
compound 4, which is scarcely soluble in Et2O was filtered, washed with Et2O
(2 ꢁ 10 mL) and dried in vacuo over CaCl2.
4-(Aryldiazenyl)chroman-4-isocyanates 5a–k: General
Procedure
A solution or suspension of compound 4 (5 mmol) dissolved or suspended
in a mixture of Et2O/CH2Cl2 (1 : 1, 70 mL) was treated with an aqueous
solution of potassium permanganate (50 mL, 2%, 6 mmol), and the mixture
was vigorously stirred for 2–3 hr at r.t. At the finish of the oxidation progress
as indicated by TLC (EtOAc/PE (60–908C) 1 : 7), the MnO2 formed was
removed by filtration with diatomaceous silica to avoid the formation of emul-
sions during the extraction process. The aqueous layer was separated and
extracted with ether (3 ꢁ 20 mL). The combined organic layers were dried
(MgSO4), filtered through a plug of silica gel and concentrated in vacuo.
The residue was pure (1H NMR) isocyanate 5 which was dried in vacuo
over CaCl2 and used without further processing.
1-Aryl-2-oxo-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo[3,2-d]
[1,5]benzoxazepines 7a–k: General Procedure
To an ice-cooled, stirred solution of compound 5 (5 mmol) in Et2O
(40 mL) was added dropwise 50% aq. HBF4 (5 mL) over a period of 5 min.
The reaction mixture was stirred at 08C for a few minutes, after which it
was diluted with CH3CN (10 mL) regardless of an occasional turbidity or pre-
cipitate. Ether was removed under reduced pressure. To ensure complete ring
expansion, the remaining solution is refluxed for 10 min and then cooled to
room temperature. After removal of the major part of CH3CN under reduced
pressure, a 2 N NaOH solution was added with stirring until permanently
basic. The reaction mixture was then diluted with water (30 mL) and extracted
with CH2Cl2 (4 ꢁ 20 mL). The combined organic layers were washed with
water, dried (MgSO4), and concentrated. The solvent was evaporated under
reduced pressure and the residue purified by recrystallization or flash
chromatography on silica gel (EtOAc) to give the pure title compound. The
homogeneity of the products was established by HPLC (Zorbax SB-C18,
5 m, 4.6 ꢁ 250 mm or 4.6 ꢁ 150 mm; mobile phase: MeOH/H2O, in 30min),
indicating a higher than 99% purity.
2-Oxo-1-phenyl-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo[3,2-d][1,5]ben-
zoxazepine (7a). Crystallization from MeOH afforded 7a as pale-yellow
crystals in 81% yield; m.p. 177–1798C. (Found: C, 68.71; H, 4.82; N,

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Li, Wang, and Tao
15.11. C16H13N3O2 requires C, 68.81%; H, 4.82%; N, 15.05%); nmax (KBr)/
cm21 3061, 2901, 1724, 1563, 1492, 1404, 1312, 1230, 1056; dH (CDCl3) 3.11
(2H, t, J 6.26, CH2), 4.76 (2H, t, J 6.28, OCH2), 6.80 (1H, d, J 8.04, 1 ꢁ Ar-
H), 7.00 (1H, dd, J 7.56, 7.56, 1 ꢁ Ar-H), 7.20–7.27 (5H, m, 5 ꢁ Ar-H),
7.34–7.37 (2H, m, 2 ꢁ Ar-H); dC (CDCl3) 163.07 (C55O), 163.04 (C55N),
148.3, 135.2, 130.0, 129.3, 128.3, 127.2, 124.9, 123.7, 123.1, 121.2 (aryl),
73.1 (OCH2), 27.5 (CH2); m/z (EI) 279 (Mþ, 100), 188 (9), 174 (45), 160
(17), 77 (9); HRMS (EI) calc. for C16H13N3O2 279.1008, found 279.1020.
9-Fluoro-2-oxo-1-phenyl-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo[3,2-d]
[1,5]benzoxazepine (7b). Crystallization from MeOH afforded 7b as white
crystals in 81% yield; m.p. 166–1688C. nmax (KBr)/cm21 3082, 2924, 1710,
1691, 1501, 1184; dH (CDCl3) 3.16 (2H, t, J 6.20, CH2), 4.74 (2H, t, J 6.10,
OCH2), 6.57 (1H, m, 1 ꢁ Ar-H), 6.93 (1H, m, 1 ꢁ Ar-H), 7.23–7.30 (4 H,
m, 4 ꢁ Ar-H), 7.38–7.41 (2H, m, 2 ꢁ Ar-H); dC (CDCl3) 163.5 (C55O),
163.0 (C55N), 158.7 (d, JC–F 980), 144.3, 135.0, 130.1, 129.4, 127.3, 124.7,
122.8, 114.7 (d, J 91), 108.4 (d, J 110) (aryl), 72.8 (OCH2), 27.4 (CH2); m/z
(EI) 297 (Mþ, 100), 255 (8), 206 (16), 192 (48), 178 (29), 149 (14), 91 (32), 77
(19); HRMS (EI) calc. for C16H12FN3O2 297.0914, found 297.0917.
9-Methyl-2-oxo-1-phenyl-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo[3,2-d]
[1,5]benzoxazepine (7c). Crystallization from MeOH afforded 7c as white
crystals in 83% yield; m.p. 183–1868C. nmax (KBr)/cm21 2926, 1701, 1593,
1504, 1381, 1344, 1222, 1036; dH (CDCl3) 2.32 (3 H, s, CH3), 2.78 (2H, t, J
6.28, CH2), 4.57 (2H, t, J 6.28, OCH2), 6.98–7.00 (2H, m, 2 ꢁ Ar-H), 7.21–
7.35 (4 H, m, 4 ꢁ Ar-H), 7.46–7.47 (2H, m, 2 ꢁ Ar-H); dC (CDCl3) 163.8
(C55O), 163.4 (C55N), 146.2, 135.7, 135.1, 129.3, 128.8, 127.1, 124.6,
122.8, 122.29, 122.27 (aryl), 73.8 (OCH2), 27.8 (CH2), 20.9 (ArCH3); m/z
(EI) 293 (Mþ, 5), 268 (100), 213 (65), 148 (33), 122 (28), 93 (80), 77 (41);
HRMS (EI) calc. for C17H15N3O2 293.1164, found 293.1169.
8-Methyl-2-oxo-1-phenyl-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo[3,2-d]
[1,5]benzoxazepine (7d). Crystallization from MeOH afforded 7d as white
crystals in 78% yield; m.p. 163–1658C. nmax (KBr)/cm21 2916, 1715,
1541, 1503, 1439, 1134; dH (CDCl3) 2.31 (3 H, s, CH3), 3.09 (2H, t, J 6.32,
CH2), 4.73 (2H, t, J 6.32, OCH2), 6.66 (1H, d, J 8.22, 1 ꢁ Ar-H), 6.79 (1H,
d, J 8.04, 1 ꢁ Ar-H), 7.08 (1H, s, 1 ꢁ Ar-H), 7.23–7.26 (3 H, m, 3 ꢁ Ar-
H), 7.34–7.37 (2H, m, 2 ꢁ Ar-H); dC (CDCl3) 163.0 (C55O), 162.6
(C55N), 148.1, 138.8, 135.1, 129.2, 127.1, 126.5, 125.5, 124.0, 123.2, 121.0
(aryl), 73.0 (OCH2), 27.4 (CH2), 20.9 (ArCH3); m/z (EI) 293 (Mþ, 85), 202
(16), 188 (100), 174 (25), 119 (13), 91 (19), 77 (22); HRMS (EI) calc. for
C17H15N3O2 293.1164, found 293.1171.
8,10-Dimethyl-2-oxo-1-phenyl-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo[3,2-d]
[1,5]benzoxazepine (7e). Crystallization from MeOH afforded 7e as white
crystals in 81% yield; m.p. 141–1438C. nmax (KBr)/cm21 3052, 2924,

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Novel Tricyclic O,N-Heterocycles
1699
1708, 1594, 1531, 1490, 1317, 1210, 1155, 1072; dH (CDCl3) 1.93 (3 H, s,
CH3), 2.31 (3 H, s, CH3), 2.89 (1H, m, CH2), 3.09 (1H, m, CH2), 4.51 (1H,
m, OCH2), 4.81 (1H, m, OCH2), 6.71 (1H, s, 1 ꢁ Ar-H), 6.96 (1H, s,
1 ꢁ Ar-H), 7.16–7.32 (5H, m, 5 ꢁ Ar-H); 55C (CDCl3) 162.7 (C55O),
160.4 (C55N), 149.9, 140.3, 135.1, 133.2, 128.9, 128.7, 127.2, 125.0, 123.2,
121.5 (aryl), 74.7 (OCH2), 26.3 (CH2), 21.0 (ArCH3), 18.2 (ArCH3);
m/z (EI) 307 (Mþ, 85), 215 (100), 202 (29), 188 (28), 173 (20), 119
(15), 91 (31), 77 (25); HRMS (EI) calc. for C18H17N3O2 307.1321, found
307.1325.
1-(4-Chlorophenyl)-2-oxo-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo[3,2-d]
[1,5]benzoxazepine (7f). Column chromatography (EtOAc) provided 7f as a
pale-yellow powder in 84% yield; m.p.150–1528C. nmax (KBr)/cm21 3064,
2897, 1712, 1537, 1494, 1028; dH (CDCl3) 3.19 (2H, t, J 5.60, CH2), 4.78
(2H, t, J 5.55, OCH2), 6.81 (1H, d, J 7.92, 1 ꢁ Ar-H), 7.05 (1H, dd, J 6.47,
6.47, 1 ꢁ Ar-H), 7.21–7.30 (4 H, m, 4 ꢁ Ar-H), 7.34 (2H, d, J 8.49,
2 ꢁ Ar-H); dC (CDCl3) 162.1 (C55O), 160.8 (C55N), 148.6, 133.5, 132.9,
129.6, 129.1, 128.4, 125.1, 125.0, 123.9, 121.8 (aryl), 73.5 (OCH2), 27.0
(CH2); m/z (EI) 313 (Mþ, 60), 297 (10), 188 (18), 174 (75), 149 (100), 125
(20), 90 (15), 71 (24); HRMS (EI) calc. for C16H12ClN3O2 313.0618, found
313.0611.
1-(4-Chlorophenyl)-9-fluoro-2-oxo-1,2,4,5-tetrahydro-1H-[1,2,4]tri-
azolo[3,2-d][1,5]benzoxazepine (7g). Column chromatography (EtOAc)
provided 7g as a white powder in 80% yield; m.p. 152–1548C. nmax (KBr)/
cm21 3070, 2898, 1710, 1551, 1488, 1092; dH (CDCl3) 3.12 (2H, t, J 6.15,
CH2), 4.72 (2H, t, J 6.20, OCH2), 6.54 (1H, dd, J 2.80, 8.20, 1 ꢁ Ar-H),
6.95 (1H, m, 1 ꢁ Ar-H), 7.20–7.27 (3 H, m, 3 ꢁ Ar-H), 7.36 (2H, d, J
8.70, 2 ꢁ Ar-H); dC (CDCl3) 164.1 (C55O), 162.8 (C55N), 158.8 (d, JC-F
982), 144.2, 133.6, 133.0, 129.9, 129.6, 124.8, 123.8, 115.0 (d, J 91), 108.2
(d, J 110) (aryl), 72.6 (OCH2), 27.4 (CH2); m/z (EI) 331 (Mþ, 12), 279
(16), 167 (43), 149 (100), 125 (8), 90 (5), 71 (19); HRMS (EI) calc. for
C16H11ClFN3O2 331.0524, found 331.0516.
1-(4-Chlorophenyl)-9-methyl-2-oxo-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo
[3,2-d][1,5]benzoxazepine (7h). Column chromatography (EtOAc) provided 7h
as a pale-yellow powder in 81% yield; m.p. 166–1688C. nmax (KBr)/cm21 2964,
2904, 1702, 1541, 1501, 1418, 1092; dH (CDCl3) 2.17 (3 H, s, CH3), 3.07 (2H, t, J
6.25, CH2), 4.70 (2H, t, J 6.25, OCH2), 6.59 (1H, s, 1 ꢁ Ar-H), 7.02 (1H, d, J 7.90,
1 ꢁ Ar-H), 7.16 (1H, d, J 8.25, 1 ꢁ Ar-H), 7.21 (2H, d, J 8.70, 2 ꢁ Ar-H), 7.33
(2H, d, J 8.75, 2 ꢁ Ar-H); dH (CDCl3) 163.5 (C55O), 163.0 (C55N), 145.9, 135.2,
133.9, 132.6, 129.4, 129.0, 128.8, 123.9, 123.4, 121.1 (aryl), 72.8 (OCH2), 27.3
(CH2), 20.8 (ArCH3); m/z (EI) 327 (Mþ, 81), 202 (29), 188 (100), 174 (31),
125 (19), 90 (22), 77 (14); HRMS (EI) calc. for C17H14ClN3O2 327.0775,
found 327.0768.

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Li, Wang, and Tao
1-(4-Chlorophenyl)-8-methyl-2-oxo-1,2,4,5-tetrahydro-1H-[1,2,4]tri-
azolo[3,2-d][1,5]benzoxazepine (7i). Column chromatography (EtOAc)
provided 7i as a pale-yellow powder in 82% yield; m.p. 141–1438C. nmax
(KBr)/cm21 3057, 2922, 1720, 1581, 1535, 1490, 1411, 1092, 1057; dH
(CDCl3) 2.32 (3 H, s, CH3), 3.09 (2H, t, J 6.30, CH2), 4.72 (2H, t, J 6.10,
OCH2), 6.65 (1H, d, J 8.17, 1 ꢁ Ar-H), 6.83 (1H, d, J 7.98, 1 ꢁ Ar-H), 7.08
(1H, d, J 0.86, 1 ꢁ Ar-H), 7.19 (2H, d, J 8.79, 2 ꢁ Ar-H), 7.32 (2H, d, J
8.80, 2 ꢁ Ar-H); dC (CDCl3) 163.2 (C55O), 162.8 (C55N), 148.1, 139.1,
133.7, 132.7, 129.4, 126.3, 125.6, 124.24, 124.22, 120.8 (aryl), 72.9 (OCH2),
27.5 (CH2), 21.0 (ArCH3); m/z (EI) 327 (Mþ, 47), 202 (21), 188 (100), 174
(32), 90 (13), 77 (12); HRMS (EI) calc. for C17H14ClN3O2 327.0775, found
327.0771.
1-(4-Chlorophenyl)-8,10-dimethyl-2-oxo-1,2,4,5-tetrahydro-1H-[1,2,4]
triazolo[3,2-d][1,5]benzoxazepine (7j). Column chromatography (EtOAc)
provided 7j as a pale-yellow powder in 79% yield; m.p. 159–1628C. nmax
(KBr)/cm21 2926, 1708, 1654, 1530, 1490, 1092; dH (CDCl3) 1.94 (3 H, s,
CH3), 2.32 (3 H, s, CH3), 2.75 (1H, m, CH2), 3.16 (1H, m, CH2), 4.51 (1H,
m, OCH2), 4.80 (1H, m, OCH2), 6.74 (1H, s, 1 ꢁ Ar-H), 6.97 (1H, s,
1 ꢁ Ar-H), 7.10 (2H, d, J 8.72, 2 ꢁ Ar-H), 7.27 (2H, d, J 8.98, 2 ꢁ Ar-H);
dC (CDCl3) 162.7 (C55O), 160.8 (C55N), 150.0, 140.7, 133.8, 133.1, 133.0
129.3, 128.9, 124.8, 124.4, 121.7 (aryl), 74.7 (OCH2), 26.3 (CH2), 21.1
(ArCH3), 18.2 (ArCH3); m/z (EI) 341 (Mþ, 60), 215 (100), 202 (36), 188
(31), 149 (28), 91 (20), 77 (17); HRMS (EI) calc. for C18H16ClN3O2
341.0931, found 341.0926.
1-(4-Bromophenyl)-2-oxo-1,2,4,5-tetrahydro-1H-[1,2,4]triazolo[3,2-d]
[1,5]benzoxazepine (7k). Column chromatography (EtOAc) provided 7k as
a pale-yellow powder in 85% yield; m.p. 142–1458C. nmax (KBr)/cm21
3060, 2962, 2911, 1721, 1587, 1549, 1489, 1426, 1309, 1234, 1059; dH
(CDCl3) 3.11 (2H, t, J 6.32, CH2), 4.75 (2H, t, J 6.32, OCH2), 6.79 (1H, d,
J 6.80, 1 ꢁ Ar-H), 7.04 (1H, m, 1 ꢁ Ar-H), 7.15 (2H, d, J 8.80, 2 ꢁ Ar-H),
7.24–7.28 (2H, m, 2 ꢁ Ar-H), 7.48 (2H, m, 2 ꢁ Ar-H); dC (CDCl3) 163.6
(C55O), 162.7 (C55N), 148.1, 134.3, 132.4, 129.1, 128.4, 125.0, 124.2,
123.8, 120.9, 120.5 (aryl), 72.8 (OCH2), 27.4 (CH2); m/z (EI) 357 (Mþ,
47), 279 (21), 188 (23), 174 (100), 160 (40), 149 (18), 90 (28), 77 (12);
HRMS (EI) calc. for C17H14BrN3O2 357.0113, found 357.0101.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support for this work from the
National Natural Science Foundation of China through grant 20372015 and
the Key Organic Synthesis Laboratory of Jiangsu Province (KJS01016).

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Received in Japan September 30, 2003

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