A straightforward preparation of benzo[f]naphtho[b][1,4]oxazepines from TNT

Article abstract of DOI:10.1016/j.tet.2008.09.090

2,4,6-Trinitrotoluene readily reacts with 1-nitroso-2-naphthol to afford 9,11-dinitrobenzo[f]naphtho[2,1-b][1,4]oxazepine. The nitro groups of the latter undergo displacement by O- and S-nucleophiles with preferential substitution of the 11-NO₂ (peri-nitro group). The structures of the substitution products are confirmed by X-ray diffraction and ¹H NMR NOE experiments.

Full text of DOI:10.1016/j.tet.2008.09.090

Tetrahedron 64 (2008) 11763–11767
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A straightforward preparation of benzo[f]naphtho[b][1,4]oxazepines from TNT
,
a
,
,
,
z
Alexander V. Samet a , Konstantine A. Kislyi z, Victor N. Marshalkin a z, Yuri A. Strelenko a
,
*
,
,
,
z
Mikhail M. Raihstat a z, Yulia V. Nelyubina b y, Victor. V. Semenova
a N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp., 119991 Moscow, Russian Federation
b A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov Street, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 July 2008
Received in revised form 5 September 2008
Accepted 25 September 2008
Available online 8 October 2008
2,4,6-Trinitrotoluene readily reacts with 1-nitroso-2-naphthol to afford 9,11-dinitrobenzo[f]naphtho[2,1-
b][1,4]oxazepine. The nitro groups of the latter undergo displacement by O- and S-nucleophiles with
preferential substitution of the 11-NO2 (peri-nitro group). The structures of the substitution products are
confirmed by X-ray diffraction and 1H NMR NOE experiments.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
2,4,6-Trinitrotoluene
1-Nitroso-2-naphthol
Benzo[f]naphtho[b][1,4]oxazepines
SNAr reactions
1. Introduction
formed), and our attempts to improve the yields by varying the
solvents (DMF, EtOH) and bases (K2CO3, NH3) failed. On the other
Previously, during the course of work aimed at the utilization of
aromatic polynitrocompounds, various benzoannulated five-, six-
and seven-membered heterocycles were prepared; some of them
possess promising biological activity.1 In particular, derivatives of
benz[d]isothiazole,2,3 quinazoline4,5 and dibenz[b,f][1,4]oxazepine6,7
were synthesized starting from 2,4,6-trinitrobenzoic acid. The latter,
in turn, was prepared by oxidation of 2,4,6-trinitrotoluene (TNT).8 In
the present work, we demonstrate that TNT itself could be used
directly for a surprisingly simple and straightforward synthesis of
benzoannulated seven-membered heterocycles, which are difficult
to prepare by other methods.9
hand, the pure products are isolated by a simple filtration in 5 min.
The reactions evidently proceed via intermediate imines of type A
with subsequent intramolecular displacement of a nitro group by
the phenolate anion (Scheme 1).
NO
-
O
OH
O2N
O2N
NO2
N
Et3N, 20 °C, 5 min
NO2
O2N
NO2
1
A
OH
NO
-
2. Results and discussion
Et3N
- NO2
We found that TNT 1 readily reacted with 1-nitroso-2-naphthol
under mild conditions in the presence of a base to yield dini-
trosubstituted benzonaphthooxazepine 2.10 The reaction of TNT
with 2-nitroso-1-naphthol under the same conditions affords an
isomeric benzonaphthooxazepine 3. Unfortunately, the yields are
only moderate at the best (significant amounts of tarry products are
NO2
NO2
N
N
O2N
O
O2N
O
3 (47%)
2 (31%)
Scheme 1.
* Corresponding author. Tel.: þ7 (495) 7161418; fax: þ7 (495) 1355328.
E-mail addresses: sametav@server.ioc.ac.ru (A.V. Samet), unelya@xrlab.ineos.
ac.ru (Y.V. Nelyubina).
The following facts provide evidence for the proposed mecha-
nistic sequence: displacement of the nitro groups in TNT by O-
nucleophiles was never reported,11 whereas the reaction of TNT
y
Fax: þ7 (495) 1355085.
z
Fax: þ7 (495) 1355328.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.09.090

11764
A.V. Samet et al. / Tetrahedron 64 (2008) 11763–11767
with aromatic nitroso compounds is known to occur readily,
affording the corresponding imines.12 To the best of our knowledge,
this approach to 1,4-oxazepine synthesis has not been described
previously: usually, the oxazepine ring is constructed from 1,4-N,O-
dinucleophilic (Nꢀ–C–C–Oꢀ) and 1,3-C,C-dielectrophilic (Cþ–C–Cþ)
fragments,13 while in the present case quite another synthetic
scheme is realized: (Nþ–C–C–Oꢀ)þ(Cꢀ–C–Cþ).14
In all cases, compounds 4 (where an 11-NO2 group is displaced)
are predominant, and this is confirmed by NOE experiments. In the
2D 1H NMR NOESY spectrum of a mixture (4aþ5a), the major iso-
mer features a cross-peak between the OCH3 protons (d 4.02) and
the aromatic proton H(10) (
the OCH3 protons and the aromatic proton H(8) (
addition, a cross-peak between the OCH3 protons and the H(12)
proton ( 9.00) is observed. A minor isomer features a cross-peak
between the OCH3 protons ( 3.91) and the two aromatic protons
H(8) and H(10) ( 7.42 and 7.54), whereas a cross-peak between the
signals of OCH3 protons and the H(12) proton ( 8.95) is not ob-
d
7.74), whereas a cross-peak between
d
7.81) is absent. In
Nitro groups in compound 2 undergo smooth displacement by
S- and O-nucleophiles under mild conditions (20 ꢁC for the S-nu-
cleophiles and 80 ꢁC for their O-counterparts), yielding both pos-
sible isomeric substitution products 4 and 5 (Scheme 2).
d
d
d
d
served. Accordingly, a structure of 4a is assigned to the major iso-
mer and a structure of 5a to the minor one (Fig. 1).
Similarly, 2D 1H NMR NOESY spectrum of a mixture (4dþ5d)
shows 4d to be a major isomer and 5d to be a minor one (Fig. 2).
The structure of compound 4b (a major product in the reaction
of 2 with 4-methylphenol) was confirmed by X-ray diffraction
(Fig. 3).
Nu
NO2
12
2
4
11
1
5
N
N
Nu-
10
3
2
+
DMF
9
O2N
Nu
O
O
8
6
4
5
Noteworthy, some substitution of both nitro groups is usually
observed in the reactiondeven if 1 equiv of nucleophile is used.
Probably, this is due to a very low solubility of the starting com-
pound 2, resulting in a local excess of the nucleophile in the re-
action mixture. To minimize bis-substitution, the nucleophile is
added in small portions under vigorous stirring. When a twofold
excess of the nucleophile is used, the bis-substitution products 6
turn to be the sole products of the reaction and are isolated in high
yields (Scheme 3).
4a, 5a: Nu = MeO (total yield 86%, isomeric ratio 4a/5a 3:1)
4b, 5b: Nu = 4-MeC6H4O (81%, 4b/5b 2:1)
4c, 5c: Nu = BuS (89%, 4c/5c 6:1)
4d, 5d: Nu = PhCH2S (85%, 4d/5d 4:1)
Scheme 2.
It is interesting to compare the selectivity observed for the nitro
group displacement in the oxazepine 2 with reactivity of the other
similar compounds. Thus, dinitrosubstituted benzoannulated five-
membered heterocycles are known to undergo selective nucleo-
philic displacement of a nitro group adjacent to a ring fusion point
(peri-nitro group),3,15–19 while in 1,3-dinitrodibenz[b,f][1,4]ox-
azepine-11(10H)-one 7 the non-adjacent nitro group (para-nitro
group) is displaced with O- and S-nucleophiles (Fig. 4).6
In order to explain these facts, it was assumed6 that steric hin-
drance of the nucleophilic attack at the peri-position, created by an
ortho-substituent, was more significant in the seven-membered
benzoannulated heterocycle than in five-membered heterocycles
(due to different geometry of the molecule) (Fig. 5).
NO2
H12
O
H10
O
N
H10
O2N
N
O
O
H8
H8
4a
5a
Figure 1. Key cross-peaks in 2D 1H NMR NOESY spectrum of 4aþ5a mixture.
NO2
S
H10
S
N
H10
O2N
N
O
O
H8
H8
4d
5d
Figure 2. Fragment of the 2D 1H NMR NOESY spectrum of 4dþ5d mixture and key cross-peaks.

A.V. Samet et al. / Tetrahedron 64 (2008) 11763–11767
11765
Nu
Nu
O
NO2
NO2
O
NH
N
R
R
O2N
Nu
O
S
O2N
Nu
7
NO2
O
NO2
R
Y
N
O2N
X
O2N
O
Figure 4. Selectivity of aromatic nitro group displacement in some benzoannulated
systems.
O
O2N
O2N
O
NH
Y
X
O2N
O
O2N
Figure 3. The general view of compound 4b in representation of atoms via thermal
ellipsoids (p¼50%).
7
Figure 5. Relative steric hindrance in some benzoannulated structures.
In this case, replacement of a C]O ortho-substituent (which is
present in compound 7) with a less bulky C–H in compound 2
should favour peri-substitutiondwhich is exactly what is observed
in the present work. Thus, the results obtained provide additional
evidence in favour of a crucial role of steric effects in nucleophilic
nitro group displacement.
approximation. The H(C) hydrogen atom positions were calculated.
All hydrogen atoms were refined in the isotropic approximation in
the riding model. For 4b the refinement converged to wR2¼0.1103
and GOF¼1.003 for all independent reflections (R1¼0.0490 was
calculated against F for 2333 observed reflections with I>2s(I)). All
calculations were performed using SHELXTL PLUS 5.0. The crys-
tallographic data have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication number
CCDC 615151 for 4b. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ,
UK (fax: þ44 (0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
3. Experimental
3.1. General
1H and 13C NMR spectra were recorded in DMSO-d6 on a Bruker
DRX500 spectrometer (500.13 MHz and 125.75 MHz, respectively);
mass-spectra were measured on a Kratos MS-30 instrument (EI,
3.3. Synthetic procedures
70 eV). IR spectra were obtained on
spectrometer.
a ‘Specord M-80-1’
3.3.1. 9,11-Dinitrodibenzo[f]naphtho[2,1-b][1,4]oxazepine (2)
To a solution of 1-nitroso-2-naphthol (3.46 g, 20 mmol) and
trinitrotoluene 1 (4.54 g, 20 mmol) in CH3CN (30 ml), Et3N (2.0 g,
20 mmol) was added dropwise with stirring. In 5 min, the resulting
precipitate was filtered off and washed with MeOH (3ꢂ10 ml). Yield
2.08 g (31%), deep-orange needles, mp 276–278 ꢁC. Found, %: C,
60.65; H, 2.58; N, 12.73. C17H9N3O5 calculated, %: C, 60.90; H, 2.71;
N,12.53. MS, m/z (I (%)): 335 [M]þ (100), 243 (68), 231 (43), 214 (41).
3.2. Crystallographic data
Crystals of 4b (C24H16N2O4, M¼369.39) are orthorhombic, space
group Pbca, at 100 K: a¼7.2939(9), b¼13.9611(14), c¼35.094(5) Å,
V¼3573.7(8) Å3,
Z¼8
(Z0¼1),
dcalcd¼1.473 g cmꢀ3
,
m
(Mo
Ka
)¼1.02 cmꢀ1, F(000)¼1648. Intensities of 10,950 reflections were
1H NMR (
8.60 (s, 1H), 8.68 (s, 1H) (both H-8 and H-10), 9.19 (s, 1H, H-12). IR
nmax, KBr): 1600, 1520, 1505, 1345, 1210, 1045.
d
, J/Hz): 7.55–7.65 (m, 3H), 7.92 (m, 2H), 8.32 (d, J¼8.4,1H),
measured with a Bruker SMART APEX2 CCD diffractometer [
l(Mo
Ka
)¼0.71072E,
u
-scans, 2
q
<54ꢁ] and 3844 independent reflections
(
[Rint¼0.0736] were used in further refinements. The structure was
solved by direct methods and refined by the full-matrix least-
squares technique against F2 in the anisotropic–isotropic
3.3.2. 9,11-Dinitrodibenzo[f]naphtho[1,2-b][1,4]oxazepine (3)
Compound 3 was prepared by the same procedure starting from
2-nitroso-1-naphthol and trinitrotoluene 1. Yield 47%, deep-orange
needles, mp 263–266 ꢁC. Found, %: C, 61.26; H, 2.88; N, 12.83.
C17H9N3O5 calculated, %: C, 60.90; H, 2.71; N, 12.53. MS, m/z (I (%)):
Nu
N
Nu- (excess)
335 [M]þ (100), 243 (48), 231 (32), 214 (26). 1H NMR (
d, J/Hz): 7.53
2
DMF, 80 °C
(d, J¼8.5, 1H), 7.60 (t, J¼8.2, 1H), 7.70 (t, J¼8.2, 1H), 7.87 (d, J¼8.0,
Nu
O
1H), 7.97 (d, J¼8.0, 1H), 8.17 (m, 2H), 8.26 (s, 1H), 9.03 (s, 1H, H-8). IR
6
(
nmax, KBr): 1600, 1525, 1500, 1340, 1205, 1045.
6a: Nu = MeO (81%)
6b: Nu = EtO (70%)
3.3.3. 11-Methoxy-9-nitrobenzo[f]naphtho[2,1-b][1,4]oxazepine
(4a) and 9-methoxy-11-nitrobenzo[f]naphtho[2,1-b][1,4]-
oxazepine (5a)
A suspension of the oxazepine 2 (0.20 g, 0.60 mmol) in dry DMF
(7 ml) was stirred at 80 ꢁC. To the mixture, a solution of Na (0.014 g,
6c: Nu = PhO (73%)
6d: Nu = 4-MeC6H4O (78%)
Scheme 3.

11766
A.V. Samet et al. / Tetrahedron 64 (2008) 11763–11767
0.62 mmol) in MeOH (5 ml) was added dropwise over 4 h. The
mixture was cooled, poured into water (50 ml) and acidified to pH 6
with HCl. The resulting precipitate was filtered off, washed with
MeOH (3ꢂ0.5 ml) and hot water (5ꢂ10 ml) and dried. Yield of the
isomeric mixture 0.165 g (86%), ratio 4a/5a 3:1. The major isomer
4a was isolated by crystallization from CH3CN (yield 51%). Yellow-
ish-brown prisms. Mp 184–187 ꢁC. Found, %: C, 67.92; H, 3.64; N,
8.33. C18H12N2O4 calculated, %: C, 67.50; H, 3.78; N, 8.75. MS, m/z (I
(%)): 320 [M]þ (100), 290 (63), 247 (61), 231 (69), 219 (72), 203 (61).
3.91; N, 6.79; S, 7.77. MS, m/z (I (%)): 412 [M]þ (16), 382 (100), 291
(10), 91 (67). 1H NMR (
, J/Hz): 4.49 (s, 2H, CH2), 7.23 (m, 3H), 7.38
d
(d, J¼8.2, 2H), 7.58 (m, 3H), 7.95 (m, 2H), 8.01 (d, J¼2.0, 1H, H-8),
8.11 (d, J¼2.0, 1H, H-10), 8.30 (d, J¼8.2, 1H), 9.01 (s, 1H, H-12). 13C
NMR (d): 37.3 (CH2), 113.1 (CH), 120.1 (CH), 120.7 (CH), 123.4 (CH),
126.4 (CH), 127.3 (CH), 127.7 (CH), 127.9 (CH), 128.7 (2CH), 129.1
(2CH), 129.9 (CH), 130.2, 131.6, 134.2, 135.8, 140.7, 147.7, 150.1, 157.4
(CH), 162.1. IR (nmax, KBr): 1605, 1520, 1500, 1350, 1235, 995, 875,
690.
1H NMR (
H-10), 7.81 (d, J¼1.9, 1H, H-8), 7.94 (m, 2H), 8.33 (d, J¼8.2, 1H), 9.00
(s, 1H, H-12). 13C NMR (
): 57.3 (OCH3), 104.0 (CH), 108.1 (CH), 120.8,
120.9 (CH),123.4 (CH), 126.3 (CH),127.3 (CH),127.9 (CH),129.8 (CH),
d, J/Hz): 4.02 (s, 3H, OMe), 7.57 (m, 3H), 7.74 (d, J¼1.9, 1H,
3.3.5. 9,11-Bis(RO)-benzo[f]naphtho[2,1-b][1,4]oxazepines (6a–d)
(general procedure)
d
A suspension of 2 (1.50 g, 4.48 mmol), the corresponding ArOH
or AlkOH (9.09 mmol or 44.8 mmol, respectively) and dried K2CO3
(1.88 g, 13.63 mmol) in dry DMF (5 ml) was stirred at 80 ꢁC for 4 h.
The mixture was cooled, poured into water (50 ml) and acidified to
pH 6 with HCl. The resulting precipitate was filtered off, washed
with MeOH (3ꢂ2 ml) and hot water (5ꢂ50 ml) and dried.
130.0, 131.6, 134.3, 147.6, 151.3, 156.7 (CH), 159.0, 162.0. IR (nmax
,
KBr): 1595, 1525, 1340, 1215, 1095.
3.3.4. Preparation of monosubstitution products 4 and 5
(general procedure)
To a stirred suspension of 2 (0.40 g, 1.19 mmol) and dried K2CO3
(0.25 g, 1.80 mmol) in dry DMF (5 ml), a solution of the corre-
sponding phenol or thiol (1.25 mmol) in DMF (2 ml) was added
dropwise over 4 h. Reaction with thiols was carried out at rt, while
p-cresol required heating at 80 ꢁC. The mixture was cooled, poured
into water (50 ml) and acidified to pH 6 with HCl. The resulting
precipitate was filtered off, washed with MeOH (3ꢂ1 ml) and hot
water (5ꢂ20 ml) and dried.
3.3.5.1. 9,11-Dimethoxybenzo[f]naphtho[2,1-b][1,4]oxazepine (6a). Yield
81%, brownish-yellow scales, mp 117–119 ꢁC (MeCN). Found, %: C,
74.62; H, 4.81; N, 4.30. C19H15NO3 calculated, %: C, 74.74; H, 4.95; N,
4.59. MS, m/z (I (%)): 305 [M]þ (100), 262 (23). 1H NMR (
d, J/Hz): 3.84 (s,
3H, OMe), 3.87 (s, 3H, OMe), 6.44 (s, 2H, H-8 and H-10), 7.31 (d, J¼8.2,
1H), 7.50 (m, 2H), 7.80 (d, J¼8.0, 1H), 7.86 (d, J¼8.2, 1H), 8.39 (d, J¼8.2,
1H), 8.78 (s, 1H, H-12). 13C NMR (
d): 55.9 (OCH3), 56.3 (OCH3), 95.5
(CH), 97.8 (CH), 109.3, 121.0 (CH), 123.5 (CH), 125.7 (CH), 126.6 (CH),
127.6 (CH), 128.4 (CH), 130.3, 131.4, 134.8, 148.0, 157.3 (CH), 159.9, 163.8,
165.0. IR (nmax, KBr): 1600, 1220, 1145, 1100.
3.3.4.1. 11-(4-Methylphenoxy)-9-nitrobenzo[f]naphtho[2,1-b][1,4]ox-
azepine (4b) and 9-(4-methylphenoxy)-11-nitrobenzo[f]naphtho[2,1-
b][1,4]oxazepine (5b). Yield of the isomeric mixture 81%, ratio 4b/
5b 2:1. The major isomer 4b was isolated by crystallization from
CH3CN (yield 42%). Orange plates, mp 156–159 ꢁC. Found, %: C,
73.01; H, 4.21; N, 7.31. C24H16N2O4 calculated, %: C, 72.72; H, 4.07; N,
7.07. MS, m/z (I (%)): 396 [M]þ (18), 379 (47), 366 (49), 349 (100). 1H
3.3.5.2. 9,11-Diethoxybenzo[f]naphtho[2,1-b][1,4]oxazepine (6b). Yield
70%, brown scales, mp 102–104 ꢁC (MeCN). Found, %: C, 75.97; H,
5.96; N, 4.58. C21H19NO3 calculated, %: C, 75.66; H, 5.74; N, 4.20. MS,
m/z (I (%)): 333 [M]þ (100), 276 (20), 248 (30). 1H NMR (
d, J/Hz): 1.39
NMR (
d
, J/Hz): 2.36 (s, 3H, Me), 7.19 (d, J¼8.1, 2H), 7.22 (d, J¼2.0, 1H,
(m, 6H, 2Me), 4.11 (m, 4H, 2CH2); 6.39 (s, 2H, H-8 and H-10), 7.30 (d,
H-10), 7.32 (d, J¼8.1, 2H), 7.56–7.65 (m, 3H), 7.92 (d, J¼2.0, 1H, H-8),
7.97 (d, J¼8.0, 1H), 8.00 (d, J¼8.2, 1H), 8.36 (d, J¼8.0, 1H), 9.19 (s, 1H,
J¼8.2, 1H), 7.50 (m, 2H), 7.78 (d, J¼8.0,1H), 7.84 (d, J¼8.0,1H), 8.40 (d,
J¼8.0, 1H), 8.77 (s, 1H, H-12). 13C NMR (
d): 14.4 (CH3), 14.5 (CH3), 64.0
H-12). 13C NMR (
d
): 19.2 (CH3), 105.9 (CH), 108.4 (CH), 119.3 (2CH),
(OCH2), 64.5 (OCH2), 96.4 (CH), 98.1 (CH), 109.3, 121.1 (CH), 123.6
(CH),125.9 (CH), 126.7 (CH), 127.7 (CH), 128.5 (CH), 130.3, 131.4,134.9,
148.0, 157.5 (CH), 159.2, 163.9, 164.3. IR (nmax, KBr): 2990, 1600, 1325,
1220, 1150, 1090, 815.
119.6 (CH), 120.8, 122.3 (CH), 125.1 (CH), 126.1 (CH), 126.6 (CH),
128.8 (CH), 128.9, 129.8 (2CH), 130.4, 133.0, 134.2, 146.4, 149.5,
150.6, 154.9 (CH), 156.4, 161.3. IR (nmax, KBr): 1600, 1530, 1500, 1345,
1215, 1045, 820.
3.3.5.3. 9,11-Diphenoxybenzo[f]naphtho[2,1-b][1,4]oxazepine (6c). Yield
73%, yellowish plates, mp 124–126 ꢁC (benzene). Found, %: C, 81.38; H,
4.39; N, 3.56. C29H19NO3 calculated, %: C, 81.10; H, 4.46; N, 3.26. MS,
3.3.4.2. 11-Butylsulfanyl-9-nitrobenzo[f]naphtho[2,1-b][1,4]oxazepi-
ne (4c) and 9-butylsulfanyl-11-nitrobenzo[f]naphtho[2,1-b][1,4]ox-
azepine (5c). Yield of the isomeric mixture 89%, ratio 4c/5c 6:1. The
major isomer 4c was isolated by crystallization from CH3CN (yield
62%). Orange plates, mp 104–106 ꢁC. Found, %: C, 66.34; H, 4.93; N,
7.12; S, 8.73. C21H18N2O3S calculated, %: C, 66.65; H, 4.79; N, 7.40; S,
8.47. MS, m/z (I (%)): 378 [M]þ (100), 348 (64), 322 (39), 292 (62),
m/z (I (%)): 429 [M]þ (100), 412 (48), 77 (78). 1H NMR (
d, J/Hz): 6.17 (s,
1H), 6.52 (s, 1H) (both H-8 and H-10), 7.06 (d, J¼8.0, 2H), 7.12 (d, J¼8.2,
2H), 7.21 (m, 2H), 7.32 (d, J¼8.2, 1H), 7.40 (m, 4H), 7.53 (m, 2H), 7.83 (d,
J¼7.8, 1H), 7.88 (d, J¼8.0, 1H), 8.38 (d, J¼8.0, 1H), 8.93 (s, 1H, H-12). 13C
NMR (d): 102.4 (CH), 103.3 (CH), 112.6, 119.8 (2CH), 120.0 (2CH), 120.9
231 (42). 1H NMR (
d
, J/Hz): 0.89 (t, J¼7.5, 3H, Me), 1.43 (m, 2H, CH2),
(CH), 123.4 (CH), 125.0 (CH), 125.1 (CH), 125.9 (CH), 126.8 (CH), 127.6
(CH), 129.0 (CH), 130.2 (4CH), 131.4, 134.4, 147.8, 154.2, 154.7, 156.5
(CH), 158.0, 162.4, 163.9. IR (nmax, KBr): 1585, 1490, 1215, 1125, 1050,
765, 695.
1.63 (m, 2H, CH2), 3.21 (t, J¼7.5, 2H, CH2), 7.57 (m, 2H), 7.62 (t, J¼8.2,
1H), 7.96 (m, 2H), 8.01 (d, J¼2.0, 1H), 8.03 (d, J¼2.0, 1H) (both H-8
and H-10), 8.31 (d, J¼8.0, 1H), 9.06 (s, 1H, H-12). 13C NMR (
d): 13.3
(CH3), 21.2 (CH2), 29.8 (CH2), 32.0 (CH2), 112.2 (CH), 118.4 (CH),
120.6 (CH), 123.2 (CH), 126.2 (CH), 127.2 (CH), 127.7 (CH), 129.4,
3.3.5.4. 9,11-Bis(4-methylphenoxy)benzo[f]naphtho[2,1-b][1,4]oxaz-
epine (6d). Yield 78%, yellowish prisms, mp 83–85 ꢁC (benzene).
Found, %: C, 81.12; H, 5.15; N, 3.36. C31H23NO3 calculated, %: C,
81.38; H, 5.07; N, 3.06. MS, m/z (I (%)): 457 [M]þ (100), 440 (78),
129.7 (CH), 131.4, 134.1, 141.4, 147.6, 150.2, 157.1 (CH), 162.1. IR (nmax
,
KBr): 2985, 1520, 1345, 1235, 810, 750.
3.3.4.3. 11-Benzylsulfanyl-9-nitrobenzo[f]naphtho[2,1-b][1,4]oxazep-
ine (4d) and 9-benzylsulfanyl-11-nitrobenzo[f]naphtho[2,1-b][1,4]-
oxazepine (5d). Pure 4d isomer precipitates from the reaction
mixture (yield 58%), and the filtrate was worked up as specified
above. Total yield of the isomeric mixture 85%, ratio 4d/5d 4:1.
Major isomer 4d: orange plates, mp 178–181 ꢁC. Found, %: C, 70.29;
H, 3.82; N, 6.97; S, 7.26. C24H16N2O3S calculated, %: C, 69.89; H,
306 (30). 1H NMR (
d, J/Hz): 2.31 (s, 6H, 2Me), 6.11 (s, 1H), 6.41 (s,
1H) (both H-8 and H-10), 6.94 (d, J¼8.2, 2H), 7.02 (d, J¼8.2, 2H),
7.20 (m, 4H), 7.30 (d, J¼8.0, 1H), 7.53 (m, 2H), 7.82 (d, J¼7.9, 1H),
7.88 (d, J¼7.9, 1H), 8.38 (d, J¼8.0, 1H), 8.92 (s, 1H, H-12). 13C NMR
(d): 20.4 (2CH3), 102.0 (CH), 102.7 (CH), 112.3, 119.9 (2CH), 120.1
(2CH), 121.0 (CH), 123.6 (CH), 126.1 (CH), 126.9 (CH), 127.8 (CH),
129.1 (CH), 130.3, 130.7 (4CH), 131.5, 134.5, 134.6, 148.0, 152.0,

A.V. Samet et al. / Tetrahedron 64 (2008) 11763–11767
11767
7. Samet, A. V.; Kislyi, K. A.; Marshalkin, V. N.; Strelenko, Y. A.; NelyubinaYu, V.;
Lyssenko, K. A.; Semenov, V. V. Russ. Chem. Bull. 2007, 56, 2089.
8. Zlotin, S. G.; Kislitsin, P. G.; Samet, A. V.; Serebryakov, E. A.; Konyushkin, L. D.;
Semenov, V. V.; Buchanan, A. C., III; Gakh, A. A. J. Org. Chem. 2000, 65, 8430.
9. For an alternative approach to benzo[f]naphtho[b][1,4]oxazepines and
biological studies, see: Nagarajan, K.; David, J.; Kulkarni, Y. S.; Hendi, S. B.;
Shenoy, S. J.; Upadhyaya, P. Eur. J. Med. Chem.dChim. Ther. 1986, 21, 21.
10. Chernysheva, N. B.; Samet, A. V.; Marshalkin, V. N.; Polukeev, V. A.; Semenov, V. V.
Mendeleev Commun. 2001, 109.
152.5, 156.7 (CH), 158.5, 162.9, 164.0. IR (nmax, KBr): 1600, 1510,
1215, 1125, 1050, 815.
Acknowledgements
This research was supported by grant from Chemical Block Ltd
(www.chemblock.com).
11. In particular, anion PhOꢀ failed to displace nitro groups in TNT: Shevelev, S. A.;
Dutov, M. D.; Serushkina, O. V. Russ. Chem. Bull. 1995, 44, 2424.
12. Sachs, F.; Kempf, R. Chem. Ber. 1902, 35, 1224.
References and notes
13. Sharp, J. T. Seven-membered Rings with Two or More Heteroatoms. In Com-
prehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon:
Oxford, 1984; Vol. 7, p 630.
14. This approach is somewhat similar to a known synthesis of dibenz[b,f]oxepines
from TNT and 2-hydroxybenzaldehydes: Hoyer, H.; Vogel, M. Monatsh. Chem.
1962, 93, 766.
1. See, for example: (a) Pullagurla, M.; Siripurapu, U.; Kolanos, R.; Bondarev, M. L.;
Dukat, M.; Setola, V.; Roth, B. L.; Glennon, R. A. Bioorg. Med. Chem. Lett. 2005, 15,
5298; (b) Samet, A. V.; Zakharov, E. P.; Semenov, V. V.; Gakh, A. A.; Buchanan, A. C.,
III. Synth. Commun. 2001, 31, 1441.
15. Fischer, W.; Kvita, V. Helv. Chim. Acta 1985, 68, 846.
2. Zlotin, S. G.; Kislitsin, P. G.; Podgursky, A. I.; Samet, A. V.; Semenov, V. V.; Bu-
chanan, A. C., III; Gakh, A. A. J. Org. Chem. 2000, 65, 8439.
3. Zlotin, S. G.; Kislitsin, P. G.; Kucherov, F. A.; Serebryakov, E. A.; Strelenko, Y. A.;
Gakh, A. A. Heterocycles 2006, 68, 2483.
16. Shevelev, S. A.; Dalinger, I. L.; Cherkasova, T. I. Tetrahedron Lett. 2001, 42, 8539.
17. Vinogradov, V. M.; Dalinger, I. L.; Starosotnikov, A. M.; Shevelev, S. A. Russ. Chem.
Bull. 2001, 50, 464.
18. Starosotnikov, A. M.; Kachala, V. V.; Lobach, A. V.; Vinogradov, V. M.; Shevelev,
S. A. Russ. Chem. Bull. 2003, 52, 1782.
19. Vorob’ev, S. S.; Dutov, M. D.; Vatsadze, I. A.; Petrosyan, E. P.; Kachala, V. V.;
Strelenko, Y. A.; Shevelev, S. A. Russ. Chem. Bull. 2007, 56, 1020.
4. Kislyi, K. A.; Samet, A. V.; Semenov, V. V. Russ. J. Org. Chem. 2006, 42, 292.
5. Kislyi, K. A.; Samet, A. V.; Strelenko, Y. A.; Semenov, V. V. J. Org. Chem. 2008, 73, 2285.
6. Samet, A. V.; Marshalkin, V. N.; Kislyi, K. A.; Chernysheva, N. B.; Strelenko, Y. A.;
Semenov, V. V. J. Org. Chem. 2005, 70, 9371.