Preparation of benzoannulated seven- and eight-membered heterocycles from 2,4,6-trinitrobenzoyl chloride

Article abstract of DOI:10.1016/j.mencom.2008.11.011

Dinitro-substituted 1,2,3-triazolo[1,5-a]dibenzo[b,f][1,4]diazepin-7-one and 10,11-dihydro-11-(4-chlorophenyl)dibenz[b,g]-[1,5]oxazocin-12-one were prepared in two steps from 2,4,6-trinitrobenzoyl chloride.

Full text of DOI:10.1016/j.mencom.2008.11.011

Mendeleev
Communications
Mendeleev Commun., 2008, 18, 320–321
Preparation of benzoannulated seven- and eight-membered
heterocycles from 2,4,6-trinitrobenzoyl chloride
Alexey N. Yamskov,† Alexander V. Samet* and Victor V. Semenov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: sametav@server.ioc.ac.ru
DOI: 10.1016/j.mencom.2008.08.011
Dinitro-substituted 1,2,3-triazolo[1,5-a]dibenzo[b,f][1,4]diazepin-7-one and 10,11-dihydro-11-(4-chlorophenyl)dibenz[b,g]-[1,5]oxazocin-
12-one were prepared in two steps from 2,4,6-trinitrobenzoyl chloride.
Intramolecular nucleophilic displacement of a nitro group in
aromatic nitro compounds is a well-known method for prepara-
tion of five- and six-membered benzoannulated heterocycles.1,2
However, this approach was rarely used for preparation of
larger heterocycles (seven- and eight-membered),1,3–5 whereas
certain classes of benzoannulated seven-membered heterocycles
(in particular, 1,4-benzodiazepines and dibenzo[b,f]azepines)
are widely used in medicine as CNS-affecting drugs (Figure 1).
N
NH2
N
N
N
H
N
N
H
O
NH
2
1
O2N
NO2
MeCN
Cl
O
NO2
3, 76%
O2N
NH
benzene
HN
OH
O
N
R
5
aqueous NH3, 50 °C
MeOH–MeCN
Sintamil (antidepressant)
Tricyclic antidepressants
Ph
Cl
O
N
NO2
Cl
N
NH
N
N
N
O2N
N
N
N
Alprazolam (tranquilizer)
O
4, 78%
Figure 1 CNS-affecting drugs.
O2N
NO2 OH
In this work aimed at the utilization of aromatic polynitro com-
pounds, we found that cyclization of ortho-nitrobenzoic acid
2-hydroxyanilides afforded dibenz[b,f][1,4]oxazepin-11(10H)-
ones.6,7 We demonstrated that intramolecular nucleophilic dis-
placement of a nitro group in 2,4,6-trinitrobenzoic acid amides A
is a general method of preparing benzoannulated seven- and eight-
membered N-containing heterocycles B (Scheme 1).
Cl
K2CO3
DMF, 50 °C
NO2
6, 86%
O
N
NO2
O2N
Scheme 2
O
7, 71%
XH
O
Cl
O
NH
O2N
NO2
O2N
NO2
NH2 XH
Cyclization of amide 3 to diazepine 4 (Scheme 2) occurs
under mild conditions‡ (MeOH–MeCN, aqueous NH3, 50 °C,
cf. ref. 6). At the same time, the conversion of amide 6 to
oxazocine 7 under these conditions failed, so in this case
the DMF/K2CO3 system7 was used instead (interestingly, the
preparation of 4 from 3 in the latter system is accompanied by
tar product formation).
NO2
NO2
NO2
O
X
1
A
base
NH
O2N
Dinitro heterocycles 4 and 7 thus prepared could serve as
starting compounds in a synthesis of various derivatives via the
selective displacement of a nitro group with different nucleo-
philes.6
B
Scheme 1
†
Deceased.
– 320 –
© 2008 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2008, 18, 320–321
6 A. V. Samet, V. N. Marshalkin, K. A. Kislyi, N. B. Chernysheva, Yu. A.
References
Strelenko and V. V. Semenov, J. Org. Chem., 2005, 70, 9371.
7 A. V. Samet, K. A. Kislyi, V. N. Marshalkin and V. V. Semenov, Izv.
Akad. Nauk, Ser. Khim., 2006, 529 (Russ. Chem. Bull., Int. Ed., 2006,
55, 549).
1 S. Radl, Adv. Heterocycl. Chem., 2002, 83, 189.
2 E. Buncel, J. Dust and F. Terrier, Chem. Rev., 1995, 95, 2261.
3 I. G. Abramov, A. V. Smirnov, S. A. Ivanovskii, M. B. Abramova, V. V.
Plakhinskii and M. S. Belyasheva, Mendeleev Commun., 2001, 80.
4 I. G. Abramov, A. V. Smirnov, L. S. Kalandadze, V. N. Sakharov and
V. V. Plakhtinskii, Heterocycles, 2003, 60, 1611.
8 M. E. Derieg and L. H. Sternbach, J. Heterocycl. Chem., 1966, 3, 237.
5 A. V. Smirnov, L. S. Kalandadze, V. N. Sakharov and M. V. Dorogov,
Mendeleev Commun., 2006, 262.
Received: 13th May 2008; Com. 08/3139
‡
1H NMR spectra were recorded in [2H6]DMSO on a Bruker DRX500
2,4,6-Trinitrobenzoic acid N-(2-hydroxybenzyl)-4-chloroanilide 6. A
solution of amine 5 (1.17 g, 5 mmol) in benzene (5 ml) was added to a
solution of 2,4,6-trinitrobenzoyl chloride 1 (0.69 g, 2.5 mmol) in benzene
(10 ml) and left overnight. The resulting precipitate was filtered off and
crystallized from MeOH. Yield 1.02 g (86%); mp 176–178 °C. 1H NMR
[10:3 mixture of (Z)- and (E)-isomers with respect to an amide N–C(O)
bond]. Major isomer, d: 5.10 (s, 2H), 6.75 (m, 2H), 7.12 (d, 2H, J 8.4 Hz),
7.21 (d, 2H, J 8.4 Hz), 7.32 (d, 1H, J 8.0 Hz), 8.94 (s, 2H), 9.38 (br. s,
1H). Minor isomer, d: 4.70 (s, 2H), 6.57 (t, 1H, J 7.8 Hz), 6.63 (d, 1H,
J 8.0 Hz), 6.97 (t, 1H, J 7.9 Hz), 7.38 (d, 2H, J 8.4 Hz), 7.52 (d, 2H,
J 8.4 Hz), 9.24 (s, 2H) (some signals overlap). Found (%): C, 51.10; H,
2.61; N, 12.09; Cl, 7.26. Calc. for C20H13ClN4O8 (%): C, 50.81; H, 2.77;
N, 11.85; Cl 7.50.
10,11-Dihydro-1,3-dinitro-11-(4-chlorophenyl)dibenz[b,g][1,5]oxazo-
cin-12-one 7. A suspension of amide 6 (0.80 g, 1.7 mmol) and dried
K2CO3 (0.28 g, 2.03 mmol) in DMF (3 ml) was stirred for 3 h at 50 °C.
The mixture was cooled, poured into 30 ml of water, acidified to pH 7,
the resulting precipitate was filtered off, washed with hot water (5 ml)
and dried. Yield 0.51 g (71%); mp 223–225 °C. 1H NMR, d: 4.76 (d, 1H,
J 10.9 Hz), 5.25 (d, 1H, J 10.9 Hz), 7.23 (m, 2H), 7.29 (d, 2H, J 8.4 Hz),
7.48 (m, 3H), 7.64 (d, 1H, J 8.1 Hz), 8.64 (s, 1H), 8.79 (s, 1H).
13C NMR, d: 52.4, 118.0, 122.3, 124.1, 126.0, 127.0, 127.4, 129.3, 130.4,
130.7, 131.6, 132.6, 139.2, 145.9, 149.6, 151.8, 154.7, 163.0. MS (ESI-MS,
MeOH), m/z (%): 873 [2M + Na]+ (100), 448 [M + Na]+ (20), 426 [M + H]+
(35). Found (%): C, 56.22; H, 3.13; N, 10.19; Cl, 8.15. Calc. for
C20H12ClN3O6 (%): C, 56.42; H, 2.84; N, 9.87; Cl, 8.33.
spectrometer (500.13 MHz), mass spectra were measured on a Finnigan
MAT LCQ instrument (ESI). Amine 5 was prepared according to a
published procedure.8
2,4,6-Trinitrobenzoic acid 1,2,3-benzotriazole-4(7)amide 3. A solution
of 4(7)-aminobenzotriazole 2 (0.54 g, 4 mmol) in MeCN (5 ml) was
added to a solution of 2,4,6-trinitrobenzoyl chloride 1 (0.55 g, 2 mmol)
in MeCN (3 ml) and left overnight. The resulting precipitate was filtered
off, the filtrate evaporated to dryness, and the residue triturated with
AcOH (2 ml), filtered, thoroughly washed with water and dried. Yield
1
0.58 g (76%); mp 184–186 °C. H NMR, d: 7.55 (br. s, 2H), 8.2 (br. s,
1H), 9.2 (br. s, 2H), 12.0 (br. s, 1H), 15.9 (br. s, 1H). Found (%): C,
42.21; H, 2.08; N, 25.90. Calc. for C13H7N7O7 (%): C, 41.83; H, 1.89;
N, 26.27.
8,10-Dinitro-1,2,3-triazolo[1,5-a]dibenzo[b,f][1,4]diazepin-7-one 4.
To a solution of amide 3 (0.50 g, 1.34 mmol) in a mixture of MeOH
(2 ml) and MeCN (2 ml), 25% aqueous NH3 (0.5 ml) was added, and the
mixture was heated at 50 °C for 48 h. The resulting glossy reddish brown
crystals were filtered off, washed with MeOH (1 ml) and dried. Yield
0.34 g (78%); mp > 300 °C (decomp.). 1H NMR, d: 7.08 (d, 1H, J 7.7 Hz),
7.40 (t, 1H, J 8.0 Hz), 7.72 (d, 1H, J 8.3 Hz), 8.54 (s, 1H), 9.04 (s, 1H),
11.29 (s, 1H). 13C NMR, d: 113.5, 114.7, 115.8, 116.6, 121.5, 124.2, 125.3,
127.2, 138.0, 147.6, 149.4, 154.1, 159.5. MS (ESI, MeOH), m/z (%): 325
[M – H]– (100), 297 [M – H – N2]– (75), 251 [M – H – N2 – NO2]– (10).
Found (%): C, 48.04; H, 1.97; N, 25.44. Calc. for C13H6N6O5 (%):
C, 47.86; H, 1.85; N, 25.76.
– 321 –