Synthesis of 4,6-dinitrobenzo[b]furans from 1,3,5-trinitrobenzene

Article abstract of DOI:10.1070/MC2005v015n05ABEH002137

O-3,5-Dinitrophenylketoximes obtained by treatment of ketoximes with 1,3,5-trinitrobenzene undergo acid-catalysed cyclization to give 4,6-dinitrobenzo[b]furans substituted at the 2- or 2- and 3-positions.

Full text of DOI:10.1070/MC2005v015n05ABEH002137

, 2005, 15(5), 202–204
Synthesis of 4,6-dinitrobenzo[b]furans from 1,3,5-trinitrobenzene
Mikhail D. Dutov, Irina A. Vatsadze, Sergei S. Vorob’ev and Svyatoslav A. Shevelev*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 095 135 5328; e-mail: shevelev@ioc.ac.ru
DOI: 10.1070/MC2005v015n05ABEH002137
O-3,5-Dinitrophenylketoximes obtained by treatment of ketoximes with 1,3,5-trinitrobenzene undergo acid-catalysed cyclization
to give 4,6-dinitrobenzo[b]furans substituted at the 2- or 2- and 3-positions.
The aim of this study was to use 1,3,5-trinitrobenzene (TNB) as
NO2
NO2
a versatile synthon prepared from 2,4,6-trinitrotoluene (TNT)
for the conversion of TNT into valuable products.1,2 TNB
can be readily obtained from TNT by a two-stage oxidative
demethylation process;3 a technologically attractive method for
the oxidation of the TNT methyl group by 80% HNO3 at elevated
temperature and pressure was proposed.4
R'
CH2R'
R''
H+
– NH4+
R''
N
O
O2N
O
O2N
1
2
TNB can add nucleophiles at the ortho position with respect
to the nitro group to give stable anionic σ-H complexes.5–8 On
the other hand, conditions have been found under which O-, S-
and N-nucleophiles of certain types replace one or more nitro
groups in TNB.9–14 The resulting substitution products can serve
for the synthesis of new polyfunctional aromatic and hetero-
cyclic structures.
a R' = H, R'' = Me
b R' = H, R'' = Ph
c R' = H, R'' = 4-BrC6H4
d R' = H, R'' = 4-FC6H4
e R' = H, R'' = 3,4-methylenedioxy-C6H3
R' = H, R'' = 4-pyridyl
f
g R' = H, R'' = 2-pyridyl
h R' = H, R'' = 2-MeOC6H4
Previously,14 we found that keto- and aldoximes replace a
nitro group in TNB in the presence of a base. Thus, a prepara-
tive method for the synthesis of hitherto unknown O-3,5-dinitro-
phenyloximes (3,5-DNPO) has been elaborated (Scheme 1).†
i
j
R' = H, R'' = 2,5-(MeO)2C6H3
R' = H, R'' = 4-HOC6H4
k R' = H, R'' = 2-furyl
R' = H, R'' = 2-thienyl
l
m R' + R'' = (CH2)4
n R' + R'' = CH2CH(Me)(CH2)2
o R' = Me, R'' = Ph
NO2
NO2
R
R
K2CO3
N
N
Scheme 2
50 °C
N-MP
(DMF)
R'
O2N
O
O2N
NO2 HO
R'
in a mixture of concentrated hydrochloric acid and acetic acid,
2:5 v/v) for oximes 1, R' = Alk. The reaction was carried out
until complete conversion of the original oxime (4–18 h); the
yields of 4,6-dinitrobenzo[b]furans 2 were 60–95%.‡
3,5-DNPO
70–95%
R, R' = H, Alk, Ar, Het
Scheme 1
This method is more general for the synthesis of 2-substituted
and 2,3-substituted 4,6-dinitrobenzo[b]furans. The synthesis of
3-substituted 4,6-dinitrobenzo[b]furans has been reported,15,16
but they were obtained by a different method. Some examples
of the synthesis of 2-substituted 4,6-dinitrobenzo[b]furans are
limited in scope.17–19
We found that O-3,5-dinitrophenylketoximes 1 containing a
methyl group (1, R' = H) or a methylene fragment (1, R' = Alk)
at the carbon atom of the C=N bond smoothly undergo cyclisa-
tion under mild conditions to give 4,6-dinitrobenzo[b]furans 2
substituted at the 2-position (from 1, R' = H) or at the 2- and
3-positions (from 1, R' = Alk) (Scheme 2).
Cyclisation was observed on heating oximes 1 (above 80 °C)
in N-MP or DMF, but the best results were obtained under
acidic catalysis: refluxing in a mixture of equal volumes of con-
centrated hydrochloric acid and ethanol for oximes 1 (R' = H);
heating (80 °C) in a mixture of equal volumes of concentrated
H2SO4 and MeCOOH for pyridine derivatives (f,g) to give
sulfates 2f,g, 1:1; somewhat more drastic conditions (refluxing
Note that the acid-catalysed benzofuranisation of O-aryloximes
is well known;20–26 it is analogous to the Fisher conversion of
N-arylhydrazones into indoles.27 However, the benzofuranisa-
tion of O-3,5-dinitrophenyloximes, which smoothly occurs under
mild conditions, is unexpected. In fact, the benzofuranisation of
O-aryloximes is assumed to occur according to the mechanism
demonstrated in Scheme 3.24,25
According to the currently accepted concept,25 the key step
of the process involves an acid-catalysed [3,3]-sigmatropic re-
arrangement of the enehydroxylamine form of an O-aryloxime
(B®C) followed by the aromatisation of a six-membered ring
†
Scheme 1 in ref. 14 contains an error: in compounds 1b–k and 2b–k,
R1 = Me.
202 Mendeleev Commun. 2005

, 2005, 15(5), 202–204
(C®D), furan ring closure (D®E) and aromatisation of the latter
by ammonium ion abstraction (E®F).
R'
R'
H
R'
X
X
X
Based on this mechanism and published data, Guzzo et al.25
concluded that electron-donating substituents in the benzene
ring should favour the [3,3]-sigmatropic rearrangement, whereas
electron-withdrawing substituents should hinder it. Although the
benzofuranisation of O-aryloximes with strong electron-with-
drawing substituents in the aryl fragment has been reported,21,23
this required rather drastic conditions in almost all the cases.
Note that the electron-withdrawing groups (NO2, CN, RSO2,
etc.) were meta with respect to the carbon atom with which the
new C–C bond was formed and that the yield of the benzo-
R''
H+
R''
NH
R''
N
NH
O
O
O
A
B
C
H
R'
H
R'
X
X
R''
R''
NH3
NH
O
OH
D
E
‡
The compounds were characterised by 1H NMR spectra, EI mass
1
R'
spectra and elemental analyses. The H NMR spectra were recorded on
X
a Bruker AC-250 spectrometer. The mass spectra were obtained using a
Kratos MS-30 instrument. The spectra of all the compounds contain
a molecular ion peak (M+). The course of the reactions was monitored
by TLC on Silufol UV-254.
R''
– NH4+
O
F
General procedure for the synthesis of 4,6-dinitrobenzo[b]furans.
0.01 mol of a corresponding 3,5-dinitrophenyloxime was added to a
mixture of ethanol (10 ml) and concentrated hydrochloric acid (36%;
10 ml) [a mixture of 10 ml of AcOH and 4 ml of conc. HCl was used
in the case of compounds m,n,o; a mixture of 5 ml of concentrated
H2SO4 and 5 ml of AcOH was used in the case of compounds f,g to give
the target compounds as sulfates (1:1) in the form of precipitates]. The
reaction mixture was refluxed (except for compounds f,g where heating
at 80 °C was used) until the entire parent dinitro compound has been
converted (TLC monitoring using CHCl3 as the eluent). The mixture was
heated to room temperature; the resulting precipitate was filtered off,
crystallised from acetonitrile and dried in vacuo (in the case of
compounds 2f and 2g, the mixture was poured into water, the resulting
precipitate of sulfate 2f or 2g was filtered off, washed with water on the
filter, dried in air and crystallised from acetonitrile).
Scheme 3
furanisation product decreased considerably in the presence of
two such groups.21,23
In this study, we were the first to perform the benzofuranisa-
tion of such O-aryloximes (under mild conditions and in high
yields) in which the formation of a new C–C bond occurs at a
carbon atom that is ortho/para with respect to strong electron-
withdrawing substituents (two nitro groups). It is likely that such
an arrangement of electron-withdrawing substituents hinders the
benzofuranisation of O-aryloximes to a smaller extent than in
the cases where such substituents are meta with respect to the
new C–C bond.
The resulting compounds are listed below.
2a: rection time, 6 h; yield 93%, mp 143–144 °C). 1H NMR, d: 8.9 (d,
1H, 4J 1.9 Hz), 8.78 (d, 1H, 4J 1.9 Hz), 7.32 (s, 1H), 2.65 (s, 3H).
2b: reaction time, 18 h; yield 95%, mp 178–179 °C. 1H NMR, d: 8.97
(d, 1H, 4J 2 Hz), 8.82 (d, 1H, 4J 2 Hz), 8.15 (m, 3H), 7.57 (m, 3H).
References
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1
2c: reaction time, 7 h; yield 77%; mp 248–249 °C. H NMR, d: 8.97
(d, 1H, 4J 2 Hz), 8.85 (d, 1H, 4J 2 Hz), 8.17 (s, 1H), 8.07 (d, 2H, 3J 8 Hz),
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4
4
3
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5
6
2g: reaction time, 10 h; yield 72% (sulfate); mp 174–175 °C. 1H NMR,
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2h: reaction time, 8 h; yield 80%; mp 227–228 °C. H NMR, d: 8.95
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7.58 (t, 1H, J 8 Hz), 7.32 (d, 1H, 3J 8 Hz), 7.21 (t, 1H, J 7.8 Hz), 4.1
3
3
8
9
(s, 3H).
1
2i: reaction time, 8 h; yield 84%; mp 252–253 °C. H NMR, d: 9.02
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4
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2j: reaction time, 12 h; yield 58%; mp 271–272 °C. 1H NMR, d: 10.3
(s, 1H), 8.8 (d, 1H, 4J 2 Hz), 8.84 (d, 1H, 4J 2 Hz), 7.93 (d, 2H, 3J 8 Hz),
7.81 (s, 1H), 6.95 (d, 2H, 3J 8 Hz).
1
2k: reaction time, 5 h; yield 75%; mp 160–161 °C. H NMR, d: 8.98
(d, 1H, J 1.9 Hz), 8.87 (d, 1H, J 1.9 Hz), 8.09 (s, 1H), 7.77 (s, 1H),
7.48 (d, 1H, J 5 Hz), 6.84 (m, 1H).
2l: reaction time, 6 h; yield 80%; mp 165–166 °C. H NMR, d: 165,
8.8 (d, 1H, J 1.9 Hz), 8.71 (d, 1H, J 1.9 Hz), 7.92 (m, 2H), 7.72 (s,
1H), 7.24 (t, 1H, J 4 Hz).
4
4
1
4
4
1
2m: reaction time, 6 h; yield 85%; mp 102 °C. H NMR, d: 8.85 (d,
1H, 4J 2 Hz), 8.7 (d, 1H, 4J 2 Hz), 2.84 (m, 4H), 1.89 (m, 4H).
2n: reaction time, 9 h; yield 71%; mp 88 °C. 1H NMR, d: 8.75 (d, 1H,
4J 2 Hz), 8.62 (d, 1H, 4J 2 Hz), 2.9 (m, 3H), 2.35 (m, 1H), 1.95 (m, 2H),
1.5 (m, 1H), 1.1 (d, 3H).
1
2o: reaction time, 6 h; yield 73%; mp 151–152 °C. H NMR, d: 8.85
(d, 1H, 4J 2 Hz), 8.7 (d, 1H, 4J 2 Hz), 7.85 (m, 2H), 7.62 (m, 3H), 2.42
(s, 3H).
Mendeleev Commun. 2005 203

, 2005, 15(5), 202–204
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Received: 8th February 2005; Com. 05/2460
204 Mendeleev Commun. 2005