,
2001, 11(3), 109–110
Synthesis of nitro-substituted benzoannelated seven-membered heterocycles from
trinitrotoluene
Natalya B. Chernysheva, Alexander V. Samet, Viktor N. Marshalkin, Valery A. Polukeev and Victor V. Semenov*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 095 135 5328
1
0.1070/MC2001v011n03ABEH001426
Dibenzo[b, f]oxepine, dibenzo[b, f]-1,4-oxazepinone and benzo[f]naphtho[2,1-b]-1,4-oxazepine were synthesised starting from
,4,6-trinitrotoluene.
2
While investigating the utilization of 2,4,6-trinitrotoluene (TNT),
it was found to be a promising starting compound for the syn-
thesis of benzoannelated five-membered heterocycles (indoles,
indazoles, benzothiophenes and benzo[d]isothiazoles).1
Probably, in both cases the methyl group of TNT reacts first
(with the C=O or N=O group of the reagent molecule) followed
by cyclization of the intermediate product via intramolecular
nucleophilic replacement of the o-nitro group by the OH group.
Substituted salicylaldehydes, as well as 2-nitroso-1-naphthol,
react in a similar way.
–4
This communication deals with the synthesis of seven-mem-
bered N- and O-containing benzoannelated heterocycles with
nitro groups at the benzene ring from TNT. These compounds
are of special interest because of their pharmaceutical activity.5,6
Thus, the antidepressant Sintamil possesses a structure of di-
Dibenzo[b, f ]-1,4-oxazepine 4 was obtained from 2,4,6-tri-
2
‡
nitrobenzoyl chloride (readily prepared from TNT ). In this
case, intermediate amide 3 can be isolated, and its cyclization to
oxazepinone 4 occurs slowly (Scheme 2).
7
benzo[b, f ]-1,4-oxazepinone:
O
COCl
NMe ·HCl
2
O N
2
N
O2N
NO2
NH2
OH
i
O
NO2
NH
Reactions of TNT with salicylaldehyde and 1-nitroso-2-naph-
thol afforded dibenzo[b,f]oxepine 1 and benzo[f]naphtho[2,1-b]-
†
1
,4-oxazepine 2, respectively (Scheme 1).
NO O
OH
2
Me
NO2
1
11
O
NH
10
O N
NO2
OH
ii
2
2
i
9
O N
2
NO2
O N
2
O
3
8
CHO
O N
O
2
4
4
NO2
TNT
6
7
1
NO2
3
NO
NO2
1
3
1
11
10
8
OH
N
Scheme 2 Reagents and conditions: i, C H , reflux, 8 h, 81%; ii, aqueous
6 6
NH , EtOH–MeCN, 50 °C, 60 h, 91%.
2
ii
TNT
9
3
3
O N
O
2
4
Dinitro-substituted compounds 1, 2 and 4 react with O- and
S-nucleophiles to yield nucleophilic substitution products in
which one or two nitro groups are replaced. These results will
be published elsewhere.
6
7
2
Scheme 1 Reagents and conditions: i, morpholine, reflux, 3 h, 75%; ii,
Et N, MeCN, 5 min, 31%.
3
References
†
1
2
H NMR spectra were recorded in [ H ]DMSO on a Bruker DRX500
6
spectrometer (500.13 MHz), mass spectra were measured on a Kratos
1 A. V. Samet, V. N. Marshalkin, S. G. Zlotin, V. V. Semenov, A. A. Gakh
and A. C. Buchanan III, 218th ACS National Meeting, New Orleans,
1
MS-30 instrument. H NMR spectra for the reaction products of TNT
1
with salicylaldehydes, 1-nitroso-2- and 2-nitroso-1-naphthols and the H
NMR spectra of the products of nucleophilic substitution in oxazepines
2
and 4 are placed on the web-site http://www.chemical-block.com.
1
,3-Dinitrodibenzo[b,f]oxepine 1: to a mixture of 10 mmol (2.27 g) of
TNT and 35 mmol (4.27 g) salicylaldehyde, morpholine (10 mol% on an
aldehyde basis) was added, and the mixture was heated for 3 h at 135 °C.
Then, the reaction mixture was cooled, dissolved in hot AcOH and
filtered. The filtrate was cooled; the precipitate was filtered off and dried.
Yield 2.13 g (75%), yellowish brown crystals, mp 148–150 °C. H NMR,
d: 7.02 (d, 1H, J 12.1 Hz), 7.29 (m, 2H), 7.43 (d, 1H, J 8.1 Hz), 7.50 (m,
‡
2,4,6-Trinitrobenzoic acid (2-hydroxyphenyl)amide 3: prepared in 81%
2
yield according to the general procedure for 2,4,6-trinitrobenzamides.
Grey powder, mp 201–203 °C. H NMR, d: 6.80–7.00 (m, 3H), 8.05 (d,
1H, J 8.3 Hz), 9.10 (s, 2H), 9.70 (br. s, 1H, OH), 10.35 (br. s, 1H, NH).
MS, m/z (%): 348 (M , 5), 153 (69), 126 (81), 108 (99), 80 (83), 79 (100).
1
1
+
2
2
H), 8.51 (s, 1H, H-2 or H-4), 8.59 (s, 1H, H-2 or H-4). MS, m/z (%):
84 (M , 15), 255 (59), 225 (53), 179 (100), 163 (61).
1,3-Dinitrodibenzo[b,f]-1,4-oxazepin-11(10H)-one 4: to a solution of
0.348 g (1 mmol) of amide 3 in a mixture of EtOH (2 ml) and MeCN
(2 ml), 7 drops of 25% aqueous NH3 were added, and the mixture
was heated for 60 h at 50 °C until the starting amide disappeared (TLC
monitoring). Then, the precipitate was filtered off, washed with EtOH
and dried. Yield 0.275 g (91%), black needles (orange needles after
chromatography on silica gel; eluent, benzene–EtOAc), mp 289–290 °C.
+
1
,3-Dinitrobenzo[f]naphtho[2,1-b]-1,4-oxazepine 2: to a solution of
0
.346 g (2 mmol) of 1-nitroso-2-naphthol and 0.454 g (2 mmol) of TNT
in 3 ml of MeCN, 0.20 g (2 mmol) of Et N was added with stirring. After
3
5
min, the precipitate was filtered off, washed with MeOH and acetone
and dried. Yield 0.208 g (31%), deeply orange crystals, mp 276–278 °C.
1
1
H NMR, d: 7.55–7.65 (m, 3H), 7.92 (m, 2H), 8.32 (d, 1H, J 8.4 Hz),
H NMR, d: 7.15–7.30 (m, 3H), 7.48 (d, 1H, H-9, J 8.5 Hz), 8.49 (s, 1H,
8
.60 (s, 1H, H-2 or H-4), 8.68 (s, 1H, H-2 or H-4), 9.19 (s, 1H, H-13).
H-2 or H-4), 8.51 (s, 1H, H-2 or H-4), 11.20 (br. s, 1H, NH). MS, m/z
(%): 301 (M , 49), 211 (32), 181 (42), 153 (57), 126 (94), 74 (100).
+
+
MS, m/z (%): 335 (M , 100), 243 (68), 231 (43), 214 (41).
–
109 –