Reactions of ortho-aminophenols and ortho-aminothiophenols with 1,3,5-trinitrobenzene

Article abstract of DOI:10.1070/MC2006v016n04ABEH002257

1,3-Dinitrophenoxazine and 1,3-dinitrophenothiazine derivatives were prepared by the reactions of ortho-aminophenols and ortho-aminothiophenols with 1,3,5-trinitrobenzene.

Full text of DOI:10.1070/MC2006v016n04ABEH002257

Mendeleev
Communications
Mendeleev Commun., 2006, 16(4), 230–232
Reactions of ortho-aminophenols and ortho-aminothiophenols with
1,3,5-trinitrobenzene
Mikhail D. Dutov, Sergei S. Vorob’ev, Ol’ga V. Serushkina, Svyatoslav A. Shevelev,* Bogdan I. Ugrak
and Vadim V. Kachala
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 495 135 5328; e-mail: shevelev@ioc.ac.ru
DOI: 10.1070/MC2006v016n04ABEH002257
1,3-Dinitrophenoxazine and 1,3-dinitrophenothiazine derivatives were prepared by the reactions of ortho-aminophenols and
ortho-aminothiophenols with 1,3,5-trinitrobenzene.
This study on the use of 1,3,5-trinitrobenzene as a multipurpose
synthon is a part of a programme for the chemical utilization of
R
O2N
NO2
HX
2,4,6-trinitrotoluene.1,2 1,3,5-Trinitrobenzene can be easily pre-
pared from 2,4,6-trinitrotoluene by two-step oxidative demethyla-
tion.3 A technologically attractive procedure for the oxidation
of the methyl group in 2,4,6-trinitrotoluene with 80% HNO3 at
elevated temperatures and pressures was proposed and optimised.4
1,3,5-Trinitrobenzene is characterised by the ability of adding
nucleophiles at the ortho/para positions with respect to nitro
groups with the formation of stable anionic σ-H complexes.5–8
At the same time, it was found that, under certain conditions, a
number of O, S, and N nucleophiles, including phenols and
thiophenols, substitute for nitro groups in 1,3,5-trinitrobenzene
in the presence of organic bases.9–14
K2CO3
+
N-MP
or DMF
(– NO2 )
H2N
NO2
X = O, S
NO2
H2N
O2N
R
H H
N
R
:B
O2N
X
O2N
X
A
B
O2N
H
N
R
In our opinion, the products of substitution for the nitro
group in 1,3,5-trinitrobenzene can be used for the synthesis of
condensed polycyclic structures. Thus, we believed that, under
conditions developed previously for phenols and thiophenols,
that is, in the presence of K2CO3 in N-MP or DMF, ortho-
aminophenols and ortho-aminothiophenols can serve as anionic
O and S nucleophiles to form substitution products A (Scheme 1).†
We believed that, under specially chosen conditions, products
A undergo intramolecular oxidative substitution for hydrogen by
the formation of cyclic σ-H complex B followed by oxidation to
target products C, that is, 1,3-dinitrophenoxazines and 1,3-di-
nitrophenothiazines (Scheme 1).
[O]
– H2O
O2N
X
C
Scheme 1
nitro compound present in the reaction mixture can serve as an
oxidizing agent.
Substituted ortho-aminophenols reacted with 1,3,5-trinitro-
benzene in a similar manner (Scheme 3); that is, the reaction
NO2
NH2
+
We found that the interaction of 1,3,5-trinitrobenzene with
ortho-aminophenol 1a in N-MP in the presence of an equimolar
amount of K2CO3 at 80 °C did not afford substitution product
2a (that is, compound A) and cyclic σ-H complex B. The only
reaction product was 1,3-dinitrophenoxazine 3a, which was isolated
in 52% yield (Scheme 2).
Thus, the reaction gave compound C (Scheme 1) without the
addition of oxidising agents. Note that atmospheric oxygen does
not act as an oxidant in this process because the same result was
obtained in a deoxygenated atmosphere. It is likely that the
process of oxidative nucleophilic substitution occurred by so-
called spontaneous or auto aromatization. At the second step, a
O2N
NO2
OH
1a
N-MP
80 °C
K2CO3
NO2
NO2
H
N
NH2
†
O
NO2
O
NO2
The reaction at the amino group is improbable because aromatic
amines did not replace a nitro group in 1,3,5-trinitrobenzene under the
specified conditions (20–80 °C).
2a
3a
Scheme 2
230 Mendeleev Commun. 2006

Mendeleev Commun., 2006, 16(4), 230–232
exhibits a general character. However, the yields of 1,3-dinitro-
NO2
phenoxazines dramatically decreased (to 11–15%)‡ on going
from compound 1a to substituted analogues.
R1
R2
NH2
OH
2-Aminopyridin-3-ol 4, a heterocyclic analogue of ortho-
aminophenol, reacted with 1,3,5-trinitrobenzene in the same
manner to give compound 5 (Scheme 4).‡
+
O2N
NO2
R3
‡
The compounds were characterised by 1H NMR spectra ([2H6]DMSO),
1a–h
a R1 = R2 = R3 = H
electron-ionization mass spectra, and elemental analysis data. The 1H NMR
spectra were measured on a Bruker AC-250 spectrometer. The mass spectra
were obtained on a Kratos MS-30 instrument. All of the compounds
exhibited peaks due to molecular ions (M+) in the mass spectra. The
course of reaction was monitored by TLC on Silufol UV-254 plates.
General procedure for the preparation of 1,3-dinitrophenoxazines 3a–h
and 5. A mixture of 2.13 g (0.01 mol) of trinitrobenzene, 1.38 g (0.01 mol)
of potassium carbonate and (0.01 mol) of o-aminophenol was placed in
7 cm3 of N-methylpyrrolidone (N-MP), heated to 80 °C and continuously
stirred until the complete conversion of trinitrobenzene (4–8 h; TLC
monitoring; eluent, CHCl3). The reaction mixture was poured into 100 cm3
of 10% HCl and stirred for 20 min; the resulting precipitate was filtered
off and dried on filter. The product was recrystallised from a minimum
amount of 1,2-dichloroethane. Compound 5 was prepared in an analogous
manner.
b R1 = Cl, R2 = R3 = H
c R1 = R3 = H, R2 = isoamyl
d R1 = R3 = Cl, R2 = Me
e R1 = SO2Et, R2 = R3 = H
f R1 = NO2, R2 = R3 = H
g R1 = R3 = H, R2 = Me
h R1 = R3 = H, R2 = NO2
NO2
H
N
R1
R2
O
NO2
R3
3a–h
Scheme 3
NO2
NO2
H
N
NH2
N
N
K2CO3
+
N-MP
OH
3a: yield 52.6%, mp 211–212 °C (lit.,16 211–212 °C). 1H NMR, d: 6.7
(m, 1H), 6.85 (m, 2H), 7.25 (m, 1H), 7.45 (d, 1H, 4J 2 Hz), 8.30 (d, 1H,
4J 2 Hz), 9.95 (s, 1H).
O2N
NO2
O
NO2
80 °C
4
5, 15%
Scheme 4
3b: yield 14%, mp 220–221 °C. 1H NMR, d: 6.7 (d, 1H, 3J 8 Hz), 6.85
3
(dd, 1H, J 8 Hz, 4J 2 Hz), 7.35 (d, 1H, 4J 2 Hz), 7.45 (d, 1H, 4J 2 Hz),
ortho-Aminothiophenols 6 analogously reacted with 1,3,5-tri-
nitrobenzene to form corresponding 1,3-dinitrophenothiazines 7
(Scheme 5).‡
8.25 (d, 1H, 4J 2 Hz), 10.0 (s, 1H).
3c: yield 12.7%, mp 175–177 °C. 1H NMR, d: 0.65 (t, 3H, 3J 8 Hz), 1.2
(s, 6H), 1.6 (q, 2H, 3J 8 Hz), 6.55 (d, 1H, 3J 8 Hz), 6.85 (d, 1H, 3J 8 Hz),
7.45 (d, 1H, 4J 2 Hz), 7.55 (d, 1H, 4J 2 Hz), 8.3 (d, 1H, 4J 2 Hz), 10.1 (s, 1H).
NO2
NO2
H
N
1
3d: yield 12.3%, mp 203–204 °C. H NMR, d: 2.22 (s, 3H), 7.4 (s,
R
+
NH2
SH
R
1H), 7.5 (d, 1H, 4J 2 Hz), 8.3 (d, 1H, 4J 2 Hz), 10.1 (s, 1H).
K2CO3
3e: yield 14.2%, mp 232–234 °C. 1H NMR, d: 1.17 (t, 3H, 3J 8 Hz), 3.22
(q, 2H, 3J 8 Hz), 6.95 (d, 1H, 3J 8 Hz), 7.35 (dd, 1H, 3J 8 Hz, 4J 2 Hz), 7.6
(d, 1H, 4J 2 Hz), 7.92 (d, 1H, 4J 2 Hz), 8.35 (d, 1H, 4J 2 Hz), 10.25 (s, 1H).
3f: yield 11.6%, mp 210–212 °C. 1H NMR, d: 6.9 (d, 1H, 3J 2 Hz), 7.5
N-MP
80 °C
O2N
NO2
S
NO2
6a R = H
6b R = CF3
7a, 38%
7b, 25%
3
4
3
4
(dd, 1H, J 8 Hz, J 2 Hz), 7.7 (d, 1H, J 8 Hz), 8.25 (d, 1H, J 2 Hz),
Scheme 5
8.35 (d, 1H, 4J 2 Hz), 10.25 (s, 1H).
3g: yield 12.1%, mp 236–237 °C. 1H NMR, d: 2.15 (s, 3H), 6.6 (d,
To determine the positions of nitro groups, we performed the
N-methylation of 1,3-dinitrophenoxazine 1a with the use of MeI
(Scheme 6). The absence of long-range interactions between the
protons of the methyl group and the protons of the dinitro-
benzene moiety in resulting compound 8 was found using two-
dimensional NMR spectroscopy. At the same time, the interac-
tion with the protons of the second ring provided support for
the structure of compound 1a: the NH fragment and the nitro
group occurred in the peri position with respect to each other.
3
3
4
1H, J 8 Hz), 6.65 (d, 1H, J 8 Hz), 7.1 (s, 1H), 7.35 (d, 1H, J 2 Hz),
8.35 (d, 1H, 4J 2 Hz), 9.9 (s, 1H).
3h: yield 11.7%, mp 207–209 °C. 1H NMR, d: 6.9 (d, 1H, 3J 8 Hz), 7.6
(d, 1H, 3J 8 Hz), 7.85 (dd, 1H, J 8 Hz, J 2 Hz), 8.25 (d, 1H, 4J 2 Hz),
3
4
8.35 (d, 1H, 4J 2 Hz), 10,25 (s, 1H).
5: yield 15.1%, mp 200–202 °C. 1H NMR, d: 6.9 (dd, 1H, 3J 8 Hz), 7.2
(d, 1H, 3J 8 Hz), 7.65 (d, 1H, 3J 8 Hz), 7.8 (d, 1H, 4J 2 Hz), 8.35 (d, 1H,
4J 2 Hz), 9.7 (s, 1H).
Synthesis of 1,3-dinitrophenothiazine 7a. A mixture of 1.5 g (0.007 mol)
of trinitrobenzene, 0.75 cm3 (0.007 mol) of 2-aminothiophenol and 0.96 g
(0.007 mol) of potassium carbonate was placed in 7 cm3 of N-methyl-
pyrrolidone. The reaction mixture was allowed to stand at room tem-
perature for 8 h (until the complete conversion of trinitrobenzene; TLC
monitoring; eluent, CHCl3). The reaction mixture was poured into
100 cm3 of 10% HCl and stirred for 20 min. The resulting precipitate
was filtered off and dried on filter. The product was recrystallised from
1,2-dichloroethane. Yield 38%, mp 192–193 °C (lit.,17 192–193 °C).
1H NMR ([2H6]DMSO) d: 7.1 (m, 4H), 8.0 (d, 1H, 4J 2 Hz), 8.5 (d, 1H,
4J 2 Hz), 10.1 (s, 1H).
Me
N
NO2
NO2
H
N
MeI
acetone, ∆
K2CO3
O
NO2
O
NO2
1a
8
Scheme 6
Note that the well-known synthesis of nitro-substituted phe-
noxazines is based on the Terpin reaction.16–18 The interaction
of picryl chloride with ortho-aminophenols and ortho-thiophenols
in the presence of bases is a convenient preparative procedure for
the preparation of various 1,3-dinitrophenoxazines and 1,3-di-
nitrophenothiazines, respectively. Here, we demonstrated a specific
feature of the chemistry of 1,3,5-trinitrobenzene: it is prone to
the reactions of oxidative nucleophilic substitution for hydrogen
without the use of external oxidizing agents, at least, in the
processes of cyclisation.
Synthesis of 1,3-dinitro-7-trifluoromethylphenothiazine 7b. A mixture
of 2.13 g (0.01 mol) of trinitrobenzene, 1.93 g (0.01 mol) of 2-amino-
4-trifluoromethylthiophenol and 1.38 g (0.01 mol) of potassium carbonate
was placed in 9 cm3 of N-methylpyrrolidone. The reaction mixture was
kept at 80 °C for 16 h (until the complete conversion of trinitrobenzene;
reaction monitoring by TLC; eluent, CHCl3). The reaction mixture was
poured into 100 cm3 of 10% HCl and stirred for 20 min. The resulting
precipitate was filtered off and dried on filter. The product was recrys-
tallised from 1,2-dichloroethane. Yield 25.6%, mp 203–204 °C (lit.,19
1
4
205–206 °C). H NMR, d: 7.25 (m, 2H), 7.55 (d, 1H, J 2 Hz), 8.1 (d,
1H, 4J 2 Hz), 8.7 (d, 1H, 4J 2 Hz), 10.12 (s, 1H).
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232 Mendeleev Commun. 2006