Stereospecific synthesis of azeto[2,1-d]-[1,5]benzothiazepin/diazepin-1-ones

Article abstract of DOI:10.1002/hc.10196

2a,4-Disubstituted 2-phenoxy-2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]benzothiazepin-1-ones and 5-benzoyl-2-phenoxy-2a,3,4,5-tetrahydro-azeto[1,2-a][1,5]benzodiazepin-1(2H)-one s were synthesized in moderate to good yields by stereospecific Staudinger cycloaddition reactions of 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepines and 1-benzoyl-2,3-dihydro-1H-1,5-benzodiazepines, respectively, with phenoxy acetyl chloride in the presence of triethylamine in anhydrous benzene.

Full text of DOI:10.1002/hc.10196

Heteroatom Chemistry
Volume 14, Number 6, 2003
Stereospecific Synthesis of Azeto[2,1-d]-
[1,5]benzothiazepin/diazepin-1-ones
Xu Huang and Jiaxi Xu
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
Department of Chemical Biology, College of Chemistry and Molecular Engineering,
Peking University, Beijing 100871, People’s Republic of China
Received 5 May 2003
penicillin, penam, and penem, have fused
ABSTRACT: 2a,4-Disubstituted 2-phenoxy-2,2a,3,4-
thiazolidine-ꢀ-lactam structures, and the effective
tetrahydro-1H-azeto[2,1-d][1,5]benzothiazepin-1-ones
antibiotics, cephalosporin and cephem, are fused
and 5-benzoyl-2-phenoxy-2a,3,4,5-tetrahydro-azeto[1,
dihydrothiazine-ꢀ-lactams [1–3]. The synthesis of
2-a][1,5]benzodiazepin-1(2H)-ones were synthesized
bicyclic ꢀ-lactams became a desirable goal based
in moderate to good yields by stereospecific Staudinger
on the discovery of penicillin and cephalosporin.
cycloaddition reactions of 2,4-disubstituted 2,3-
Although a lot of the penicillin- and cephalosporin-
dihydro-1,5-benzothiazepines and 1-benzoyl-2,3-dihy-
like compounds have been obtained by biosynthesis
dro-1H-1,5-benzodiazepines, respectively, with phe-
or chemical synthesis [4,5], it seemed to be necessary
noxy acetyl chloride in the presence of triethylamine
to synthesize some novel compounds with a fused
ꢀ
C
in anhydrous benzene.
2003 Wiley Periodicals, Inc.
ꢀ-lactam-heterocyclic ring for bioassay of antibac-
terial activity because of the growing resistance of
bacteria against penicillin- and cephalosporin-like
compounds and the requirement for medicines with
a more specific antibacterial activity. Some ꢀ-lactam
derivatives have also been recognized as inhibitors
of human leukocytase elastase [6] and serine pro-
tease [7,8]. Till now, numerous ꢀ-lactam derivatives
of thiazoline and dihydrothiazine, containing a five-
and six-membered sulfur and nitrogen-containing
heterocyclic ring, respectively, have been synthe-
sized by various methods [9–11]. In recent years,
our working group has paid much attention to
the synthesis and stereostructure investigation of
tricyclic derivatives of benzothiazepines and ben-
zodiazepines because of their potential biological
and pharmaceutical importance [12–16]. Herein
we report the synthesis of ꢀ-lactam derivatives of
2,3-dihydro-1,5-benzothiazepine, having a seven-
membered sulfur- and nitrogen-containing hete-
rocyclic ring, and 2,3-dihydro-1,5-benzodiazepine,
with a seven-membered two nitrogen-containing
heterocyclic ring, for pharmaceutical research.
Heteroatom Chem 14:564–569, 2003; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.10196
INTRODUCTION
The ꢀ-lactam (2-azetidinone) skeleton has gained
significant interest among synthetic as well as
medicinal chemists over the years, mainly because
it represents the key structural element of synthetic
and natural antibiotics. Most of the important
antibiotics possess the representative structure of
a ꢀ-lactam fused to a five- or six-membered hete-
rocyclic ring containing nitrogen and sulfur atoms
[1–3]. For instance, the effective antibiotics,
Correspondence to: Jiaxi Xu; e-mail: jxxu@chem.pku.edu.cn.
Contract grant sponsor: National Natural Science Foundation
of China.
Contract grant number: 20272002.
Contract grant sponsor: Ministry of Education of China.
Contract grant sponsor: Peking University.
c
ꢀ
2003 Wiley Periodicals, Inc.
564

Specific Synthesis of Azeto[2,1-d][1,5]benzothia/diazepin-1-ones 565
TABLE
1 Synthesis of 2a,4-Disubstituted 2-Phenoxy-
RESULTS AND DISCUSSION
tetrahydro-1H-azeto[1,2-a][1,5]benzothiazepin-1-ones 2a–h
and Azeto[1,2-a][1,5]benzodiazepin-1(2H)-ones 2i–p
The most popular methods for the preparation
of the ꢀ-lactam ring involves the Staudinger cy-
cloaddition of imines to ketenes, the enolate–
imine condensations and subsequent ring-closure of
ꢀ-amino esters, the ketene–imine cycloaddition us-
ing metallo-carbene intermediates, and the annela-
tion of aziridines by use of transition-metal cata-
lysts [4,5]. The Staudinger cycloaddition of imines
to ketenes is probably the most important method
among the above-mentioned strategies.
Till now, a few examples of ꢀ-lactam deriva-
tives of benzothiazepines and benzodiazepines have
been prepared by us and others [17–23]. As a
continuation of our efforts into the preparation
of structurally diverse ꢀ-lactam derivatives of 1,5-
benzoheteroazepines, herein we report synthesis
of 2-phenoxy 1H-azeto[2,1-d][1,5]benzothiazepin-
1-ones and azeto[1,2-a][1,5]benzodiazepin-1(2H)-
ones.
2a,4-Disubstituted 2-chloro- and 2,2-dichloro-2,
2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5] benzothia-
zepin-1-ones and 2a,4-disubstituted 5-benzoyl-2-
phthalimido-2a,3,4,5-tetrahydro-azeto[1,2-a][1,5]
benzodiazepin-1(2H)-ones were prepared previously
by us. To build up a structurally devise ꢀ-lactam
derivative library of 1,5-benzoheteroazepine,
2-phenoxy ꢀ-lactam derivatives of 1,5-benzothiaze-
pine, and 1H-1,5-benzodiazepines, 2a,4-disubsti-
tuted 2-phenoxy 2,2a,3,4-tetrahydro-1H-azeto[2,
1-d][1,5]benzothiazepin-1-ones 2a–h and 5-benzoyl-
2a,3,4,5-tetrahydro-azeto[1,2-a][1,5]benzodiazepin-
1(2H)-ones 2i–p were prepared from phenoxyacetyl
chloride with 1,5-benzothiazepine 1a–h and 1H-1,
5-benzodiazepines 1i–p, respectively, in the presence
of triethylamine in anhydrous benzene in moderate
to good yields (Scheme 1, Table 1).
X
R1
R2
Yield (%) mp (◦C)
2a
2b
2c
2d
2e
2f
S
S
S
S
S
S
S
Me
Me
Me
Ph
4-MePh
4-MeOPh
Ph
90
80
75
93
29
87
64
40
88
57
95
81
92
83
51
33
179–180
165–166
155–156
190–191
179–180
220–222
239–240
195–196
248–249
183–184
226–227
209–210
235–236
191–192
183–184
249–250
Ph
2-ClPh
4-ClPh
4-BrPh
Ph
Me
Me
Ph
Ph
Ph
2g
2h
2i
S
4-ClPh
4-MePh
4-MeOPh
Ph
PhCON
PhCON
2j
2k PhCON
2l
Ph
PhCON
3-ClPh
4-ClPh
3-BrPh
Ph
Ph
Ph
Ph
2m PhCON
2m PhCON
2o PhCON 4-MeOPh
2p PhCON Ph
4-ClPh
the cycloaddition reaction is stereospecific as those
in the reactions of 1,5-benzoheteroazepines with
chloroacetyl chloride and phthalimidoacetyl chlo-
ride, which were discussed in our previous papers
[22,23]. The process of the stereospecific cycload-
dition is depicted in Scheme 2. 2,4-Disubstituted
2,3-dihydro-1,5-benzoheteroazepines 1
adopt a
boat-like conformation [24]. They react with phe-
noxyketene, generated from phenoxyacetyl chloride
with triethylamine, to form zwitterionic intermedi-
ates 3 from the less hindered side of the ketene over
the small group H [25,26]. The intermediates 3 then
undergo a conrotatory ring closure in the downward
direction, in which the whole azepine ring rotates
downwards, to yield a ꢀ-lactam ring from the outside
of the azepine ring. Thus, only one pair of diastere-
omers of each cycloadduct, with shown stereoconfig-
uration, was obtained in the cycloaddition reaction.
In summary, 2a,4-disubstituted 2-phenoxy-2,
2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]benzothiaze-
pin-1-ones and 5-benzoyl-2-phenoxy-2a,3,4,5-tetra-
hydro-azeto[1,2-a][1,5]benzodiazepin-1(2H)-ones
were synthesized in moderate to good yields
by Staudinger cycloaddition reactions of 2,4-
disubstituted 2,3-dihydro-1,5-benzothiazepines and
1-benzoyl-2,3-dihydro-1H-1,5-benzodiazepines, res-
pectively, with phenoxy acetyl chloride in the pres-
ence of triethylamine in anhydrous benzene. The
cycloaddition reaction is stereospecific.
The structures of all products were confirmed by
1H NMR, IR, MS, and elemental analyses. In their
1H NMR spectra, ꢀ-lactam derivatives show a char-
acteristic singlet of the azetidinone ring proton at
δ-5.21–5.40 ppm. According to their H NMR spec-
tra, only one pair of enantiomers was found in each
of the cycloaddition reactions. This indicates that
1
EXPERIMENTAL
Melting points were obtained on a Yanaco melt-
ing point apparatus and are uncorrected. Elemental
analyses were carried out on an Elementar Vario
SCHEME 1 Synthesis of 2a,4-disubstituted 2-phenoxy-
tetrahydro-1H-azeto[1,2-a][1,5]benzothiazepin-1-ones and
azeto[1,2-a][1,5]benzodiazepin-1(2H)-ones.

566 Huang and Xu
SCHEME 2 Stereospecificity in the cycloaddition reaction.
1
NMR (300 MHz, CDCl3) δ 7.97–6.73 (m, 14H, ArH),
5.31 (s, 1H, CH), 3.35 (dd, J = 1.2, 14.4 Hz, 1H, H
in CH2), 2.99 (ddq, J = 1.2, 10.8, 7.2 Hz, 1H, CH),
2.63 (dd, J = 10.8, 14.4 Hz, 1H, H in CH2), 1.43
(d, J = 7.2 Hz, 3H, CH3); IR (KBr): ν1763 (C O)
cm−1; EI-MS (m/z): 387 (M+, 25), 294 (M PhO,
21), 293 (M PhOH, 34), 253 (M PhOCHCO, 83),
211 (100); Anal. Calcd for C24H21NO2S (387.49): C,
74.39; H, 5.46; N, 3.61. Found: C, 74.22; H, 5.57;
N, 3.75.
EL elemental analyzer. The H NMR spectra were
recorded on a Varian Mercury 300 spectrometer with
TMS as an internal standard in the CDCl3 solution.
The IR spectra were taken on a Brucker Vector 22
FT-IR spectrophotometer in KBr. Mass spectra were
obtained on a VG ZAB-HS mass spectrometer. TLC
separations were performed on silica gel G plates
with petroleum ether (60–90◦C)/ethyl acetate (5:1),
and the plates were visualized with UV light.
Synthesis of 2a,4-disubstituted
2-phenoxy-2,2a,3,4-tetrahydro-1H-azeto[2,1-d]-
[1,5]benzothiazepin-1-ones 2a–h
and 2a,4-disubstituted 5-benzoyl-2-
phenoxy-2a,3,4,5-tetrahydro-azeto[2,1-d]-
[1,5]benzodiazepin-1(2H)-ones 2i–p
4-Methyl-2a-(4-methylphenyl)-2-phenoxy-2,
2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]-
benzothiazepin-1-one (2b)
Colorless crystal, yield 80%, mp 165–166◦C. Rf 0.40
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
General Procedure. To
a
solution of 1,5-
NMR (200 MHz, CDCl3) δ 7.96–6.75 (m, 13H, ArH),
5.27 (s, 1H, CH), 3.32 (d, J = 14.1 Hz, 1H, H in
CH2), 3.00 (dq, J = 10.8, 6.8 Hz, 1H, CH), 2.60 (dd,
J = 10.8, 14.1 Hz, 1H, H in CH2), 2.24 (s, 3H, CH3),
1.43 (d, J = 6.8 Hz, 3H, CH3); IR (KBr): ν1763 (C O)
cm−1; EI-MS (m/z): 401 (M+, 2.9), 308 (M PhO,
3.5), 307 (M PhOH, 5.8), 267 (M PhOCHCO, 8.7),
225 (10); Anal. Calcd for C25H23NO2S (401.52): C,
74.78; H, 5.77; N, 3.49. Found: C, 74.50; H, 5.88;
N, 3.50.
benzothiazepine (or 1-benzoyl-1,5-benzodiazepine)
1 (1 mmol) and phenoxyacetyl chloride (0.268 g,
2 mmol) in anhydrous benzene (20 ml) was added
dropwise dried triethylamine (0.222 g, 2.2 mmol)
in anhydrous benzene (10 ml) under stirring at
room temperature over a period of 20 min. Af-
ter having been stirred for 4 h at room tempera-
ture, for 1-benzoyl-1,5-benzodiazepine 1i–p, at re-
fluxing, the crystalline triethylamine hydrochloride
that had formed was removed by filtration, and the
benzene solution was washed with water, saturated
aqueous NaHCO3, and brine, and then dried over
Na2SO4. After removal of the solvent, the resulting
residue was recrystallized from ethanol to yield col-
orless crystals 2 except for 2h, 2o, and 2p, which
were obtained through a silica gel column with
petroleum ether (60–90◦C)/ethyl acetate (5:1) as an
eluent.
4-Methyl-2a-(4-methoxylphenyl)-2-phenoxy-
2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]-
benzothiazepin-1-one (2c)
Colorless crystal, yield 75%, mp 155–156◦C. Rf 0.40
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 7.94–6.73 (m, 13H, ArH),
5.27 (s, 1H, CH), 3.69 (s, 3H, CH3O), 3.30 (d, J = 14.1
Hz, 1H, H in CH2), 3.01 (dq, J = 10.5, 6.9 Hz, 1H,
CH), 2.60 (dd, J = 10.5, 14.1 Hz, 1H, H in CH2), 1.43
(d, J = 6.9 Hz, 3H, CH3); IR (KBr): ν 1761 (C O)
cm−1; EI-MS (m/z): 417 (M+, 15), 324 (M PhO, 12),
323 (M PhOH, 23), 283 (M PhOCHCO, 64), 241
(63); Anal. Calcd for C25H23NO3S (417.52): C, 71.92;
H, 5.55; N, 3.35. Found: C, 72.08; H, 5.60; N, 3.49.
4-Methyl-2-phenoxy-2a-phenyl-2,2a,3,4-
tetrahydro-1H-azeto[2,1-d][1,5]-
benzothiazepin-1-one (2a)
Colorless crystal, yield 90%, mp 179–180◦C. Rf 0.40
1
(petroleum ether AcOEt = 5:1, silica gel plate). H

Specific Synthesis of Azeto[2,1-d][1,5]benzothia/diazepin-1-ones 567
EI-MS (m/z): 527 (M+, 4.0), 434 (M PhO, 3.1), 433
(M PhOH, 6.5), 393 (M PhOCHCO, 0.6), 211 (100);
Anal. Calcd for C29H22BrNO2S (528.46): C, 65.91; H,
4.20; N, 2.65. Found: C, 65.99; H, 4.29; N, 2.58.
2-Phenoxy-2a,4-diphenyl-2,2a,3,4-tetrahydro-1H-
azeto[2,1-d][1,5]benzothiazepin-1-one (2d)
Colorless crystal, yield 93%, mp 190–191◦C. Rf 0.40
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.04–6.68 (m, 19H, ArH),
5.39 (s, 1H, CH), 4.02 (d, J = 11.0 Hz, 1H, H in CH2),
3.67 (d, J = 14.0 Hz, 1H, CH), 3.22 (dd, J = 11.0,
14.0 Hz, 1H, H in CH2); IR (KBr): ν1765 (C O) cm−1;
EI-MS (m/z): 449 (M+, 16), 356 (M PhO, 7.1), 355
(M PhOH, 16), 315 (M PhOCHCO, 2.9), 211 (100);
Anal. Calcd for C29H23NO2S (449.56): C, 77.48; H,
5.16; N, 3.12. Found: C, 77.47; H, 5.09; N, 3.20.
2a-(4-Chlorophenyl)-2-phenoxy-4-phenyl-
2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]-
benzothiazepin-1-one (2h)
Colorless crystal, yield 40%, mp 195–196◦C. Rf 0.30
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.00–6.71 (m, 18H, ArH),
5.39 (s, 1H, CH), 3.95 (d, J = 11.0 Hz, 1H, H in CH2),
3.60 (d, J = 14.2 Hz, 1H, CH), 3.22 (dd, J = 11.0,
14.2 Hz, 1H, H in CH2); IR (KBr): ν 1766 (C O) cm−1;
EI-MS (m/z): 483 (M+, 6.9), 390 (M PhO, 3.1), 389
(M PhOH, 6.9), 349 (M PhOCHCO, 2.4), 245 (59);
Anal. Calcd for C29H22ClNO2S (484.01): C, 71.96; H,
4.58; N, 2.89. Found: C, 72.18; H, 4.50; N, 2.78.
4-(2-Chlorophenyl)-2-phenoxy-2a-phenyl-
2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]-
benzothiazepin-1-one (2e)
Colorless crystal, yield 29%, mp 179–180◦C. Rf 0.30
(petroleum ether AcOEt = 5:1, silica gel plate).
1H NMR (300 MHz, CDCl3) δ 8.03–6.65 (m, 18H,
ArH), 5.40 (s, 1H, CH), 4.54 (dd, J = 0.9, 10.6 Hz,
1H, H in CH2), 3.58 (dd, J = 0.9, 14.1 Hz, 1H,
CH), 3.22 (dd, J = 10.6, 14.1 Hz, 1H, H in CH2);
IR (KBr): ν 1764 (C O) cm−1; EI-MS (m/z): 483
(M+, 8.8), 390 (M PhO, 5.9), 389 (M PhOH, 13),
349 (M PhOCHCO, 5.5), 211 (100); Anal. Calcd for
C29H22ClNO2S (484.01): C, 71.96; H, 4.58; N, 2.89.
Found: C, 72.11; H, 4.77; N, 3.00.
5-Benzoyl-4-methyl-2a-(4-methylphenyl)-
2-phenoxy-2a,3,4,5-tetrahydro-azeto[1,2-a]-
[1,5]benzodiazepin-1(2H)-one (2i)
Colorless crystal, yield 88%, mp 248–249◦C. Rf 0.40
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.50–6.39 (m, 18H, ArH),
5.33 (ddq, J = 7.5, 10.5, 6.6 Hz, 1H, CH), 5.21 (s,
1H, CH), 3.30 (dd, J=7.5, 14.5 Hz, 1H, H in CH2),
2.25 (dd, J=10.5, 14.5 Hz, 1H, H in CH2), 2.15 (s,
3H, CH3), 1.24 (d, J = 6.6 Hz, 3H, CH3); IR (KBr):
ν 1762, 1644 (C O) cm−1; EI-MS (m/z): 488 (M+,
0.4), 395 (M PhO, 8.6), 394 (M PhOH, 6.6), 354
(M PhOCHCO, 2.5); Anal. Calcd for C32H28N2O3
(488.58): C, 78.67; H, 5.78; N, 5.73. Found: C, 78.82;
H, 5.91; N, 5.94.
4-(4-Chlorophenyl)-2-phenoxy-2a-phenyl-
2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]-
benzothiazepin-1-one (2f)
Colorless crystal, yield 87%, mp 220–222◦C. Rf 0.30
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.04–6.69 (m, 18H, ArH),
5.39 (s, 1H, CH), 3.98 (d, J = 11.0 Hz, 1H, H in CH2),
3.62 (d, J = 14.1 Hz, 1H, CH), 3.17 (dd, J = 11.0,
14.1 Hz, 1H, H in CH2); IR (KBr): ν 1764 (C O) cm−1;
EI-MS (m/z): 483 (M+, 6.5), 390 (M PhO, 4.9), 389
(M PhOH, 9.1), 349 (M PhOCHCO, 1.0), 211 (100);
Anal. Calcd for C29H22ClNO2S (484.01): C, 71.96; H,
4.58; N, 2.89. Found: C, 71.95; H, 4.66; N, 2.99.
5-Benzoyl-4-methyl-2a-(4-methoxylphenyl)-
2-phenoxy-2a,3,4,5-tetrahydro-azeto[1,2-a]-
[1,5]benzodiazepin-1(2H)-one (2j)
Colorless crystal, yield 57%, mp 183–184◦C. Rf 0.30
(petroleum ether AcOEt = 3:1, silica gel plate).
1H NMR (300 MHz, CDCl3) δ 8.50–6.39 (m, 18H,
ArH), 5.35 (ddq, J = 8.4, 9.9, 6.6 Hz, 1H, CH), 5.21
(s, 1H, CH), 3.62 (s, 3H, CH3), 3.30 (dd, J = 8.4,
15.0 Hz, 1H, H in CH2), 2.26 (dd, J=9.9, 15.0 Hz,
1H, H in CH2), 1.25 (d, J = 6.6 Hz, 3H, CH3); IR
(KBr): ν 1761, 1644 (C O) cm−1; EI-MS (m/z): 504
(M+, 0.6), 411 (M PhO, 20), 410 (M PhOH, 16),
370 (M PhOCHCO, 23); Anal. Calcd for C32H28N2O4
(504.58): C, 76.17; H, 5.59; N, 5.55. Found: C, 76.44;
H, 5.66; N, 5.69.
4-(4-Bromophenyl)-2-phenoxy-2a-phenyl-
2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]-
benzothiazepin-1-one (2g)
Colorless crystal, yield 64%, mp 239–240◦C. Rf 0.30
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.04–6.69 (m, 18H, ArH),
5.39 (s, 1H, CH), 3.96 (d, J = 10.8 Hz, 1H, H in CH2),
3.61 (d, J = 14.0 Hz, 1H, CH), 3.17 (dd, J = 10.8,
14.0 Hz, 1H, H in CH2); IR (KBr): ν 1765 (C O) cm−1;

568 Huang and Xu
6.22 (dd, J = 7.8, 12.0 Hz, 1H, CH), 5.37 (s, 1H,
CH), 3.46 (dd, J = 7.8, 15.0 Hz, 1H, H in CH2), 2.90
(dd, J = 12.0, 15.0 Hz, 1H, H in CH2); IR (KBr):
ν 1763, 1645 (C O) cm−1; EI-MS (m/z): 614 (M+,
1.8), 521 (M PhO, 14), 520 (M PhOH, 9.6), 480
(M PhOCHCO, 2.1); Anal. Calcd for C36H27BrN2O3
(615.52): C, 70.25; H, 4.42; N, 4.55. Found: C, 70.01;
H, 4.54; N, 4.69.
5-Benzoyl-2-phenoxy-2a,4-diphenyl-
2a,3,4,5-tetrahydro-azeto[1,2-a][1,5]-
benzodiazepin-1(2H)-one (2k)
Colorless crystal, yield 95%, mp 226–227◦C. Rf 0.50
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.57–6.27 (m, 24H, ArH),
6.07 (d, J = 7.8 Hz, 1H, CH), 5.37 (s, 1H, CH),
3.48 (dd, J = 7.8, 15.0 Hz, 1H, H in CH2), 2.96
(dd, J = 12.0, 15.0 Hz, 1H, H in CH2); IR (KBr):
ν 1763, 1647 (C O) cm−1; EI-MS (m/z): 536 (M+,
1.6), 443 (M PhO, 11), 442 (M PhOH, 7.3), 402
(M PhOCHCO, 1.8); Anal. Calcd for C36H28N2O3
(536.62): C, 80.58; H, 5.26; N, 5.22. Found: C, 80.39;
H, 5.09; N, 5.41.
5-Benzoyl-4-(4-methoxylphenyl)-2-phenoxy-
2a-phenyl-2a,3,4,5-tetrahydro-azeto[1,2-a]-
[1,5]benzodiazepin-1(2H)-one (2o)
Colorless crystal, yield 51%, mp 183–184◦C. Rf 0.20
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.56–6.03 (m, 23H, ArH),
6.27 (dd, J = 7.8, 12.0 Hz, 1H, CH), 5.36 (s, 1H, CH),
3.76 (s, 3H, CH3O), 3.44 (dd, J = 7.8, 15.0 Hz, 1H, H
in CH2), 2.93 (dd, J = 12.0, 15.0 Hz, 1H, H in CH2);
IR (KBr): ν 1762, 1646 (C O) cm−1; EI-MS (m/z):
566 (M+, 2.6), 473 (M PhO, 11), 472 (M PhOH, 6.0),
432 (M PhOCHCO, 3.4); Anal. Calcd for C37H30N2O4
(566.65): C, 78.43; H, 5.34; N, 4.94. Found: C, 78.21;
H, 5.30; N, 5.12.
5-Benzoyl-4-(3-chlorophenyl)-2-phenoxy-
2a-phenyl-2a,3,4,5-tetrahydro-azeto[1,2-a]-
[1,5]benzodiazepin-1(2H)-one (2l)
Colorless crystal, yield 81%, mp 209–210◦C. Rf 0.30
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.58–6.10 (m, 23H, ArH),
6.23 (dd, J = 11.8, 7.8 Hz, 1H, CH), 5.37 (s, 1H,
CH), 3.47 (dd, J = 7.0, 14.8 Hz, 1H, H in CH2), 2.91
(dd, J = 11.8, 14.8 Hz, 1H, H in CH2); IR (KBr):
ν 1763, 1645 (C O) cm−1; EI-MS (m/z): 570 (M+,
0.6), 477 (M PhO, 3.0), 476 (M PhOH, 2.3), 436
(M PhOCHCO, 2.7); Anal. Calcd for C36H27ClN2O3
(571.06): C, 75.72; H, 4.77; N, 4.91. Found: C, 75.70;
H, 5.01; N, 4.80.
5-Benzoyl-2a-(4-chlorophenyl)-2-phenoxy-
4-phenyl-2a,3,4,5-tetrahydro-azeto[1,2-a]-
[1,5]benzodiazepin-1(2H)-one (2p)
Colorless crystal, yield 33%, mp 249–250◦C. Rf 0.30
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (300 MHz, CDCl3) δ 8.55–6.07 (m, 23H, ArH),
6.25 (dd, J = 7.8, 11.2 Hz, 1H, CH), 5.36 (s, 1H,
CH), 3.43 (dd, J = 7.8, 14.7 Hz, 1H, H in CH2), 2.97
(dd, J = 11.2, 14.7 Hz, 1H, H in CH2); IR (KBr):
ν 1765, 1642 (C O) cm−1; EI-MS (m/z): 570 (M+,
2.6), 477 (M PhO, 14), 476 (M PhOH, 21), 436
(M PhOCHCO, 3.8); Anal. Calcd for C36H27ClN2O3
(571.06): C, 75.72; H, 4.77; N, 4.91. Found: C, 75.91;
H, 4.57; N, 5.14.
5-Benzoyl-4-(4-chlorophenyl)-2-phenoxy-
2a-phenyl-2a,3,4,5-tetrahydro-azeto[1,2-a]-
[1,5]benzodiazepin-1(2H)-one (2m)
Colorless crystal, yield 92%, mp 235–236◦C. Rf 0.30
1
(petroleum ether AcOEt = 5:1, silica gel plate). H
NMR (200 M Hz, CDCl3) δ 8.58–6.03 (m, 23H, ArH),
6.23 (dd, J = 7.8, 11.6 Hz, 1H, CH), 5.37 (s, 1H,
CH), 3.44 (dd, J = 7.8, 14.9 Hz, 1H, H in CH2), 2.90
(dd, J = 11.6, 14.9 Hz, 1H, H in CH2); IR (KBr):
ν 1763, 1643 (C O) cm−1; EI-MS (m/z): 570 (M+,
3.5), 477 (M PhO, 28), 476 (M PhOH, 19), 436
(M PhOCHCO, 3.0); Anal. Calcd for C36H27ClN2O3
(571.06): C, 75.72; H, 4.77; N, 4.91. Found: C, 75.51;
H, 4.49; N, 5.08.
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1
(petroleum ether AcOEt = 5:1, silica gel plate). H
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