Unexpected formation of 6-[benzofuran-3(2H)-ylidene]-3,3a,9,9a-tetra- hydroimidazo[4,5-e]thiazolo[3,2-b][1,2,4]triazine-2,7-dione derivative

Article abstract of DOI:10.1016/j.mencom.2015.11.027

Condensation of 4,6-di(tert-butyl)-3-nitro-1,2-benzoquinone with 1,3-dimethyl-3a,9a-diphenyl-3,3a,9,9a-tetrahydroimidazo[4,5-e]- thiazolo[3,2-b][1,2,4]triazine-2,7(1H,6H)-dione in AcOH gives a new 6-(benzofuranylidene)tetrahydroimidazo[4,5-e]thiazolo[3,2-

Full text of DOI:10.1016/j.mencom.2015.11.027

Mendeleev
Communications
Mendeleev Commun., 2015, 25, 476–478
Unexpected formation of 6-[benzofuran-3(2H)-ylidene]-3,3a,9,9a-tetra-
hydroimidazo[4,5-e]thiazolo[3,2-b][1,2,4]triazine-2,7-dione derivative
Angelina N. Kravchenko,*a Sergei V. Vasilevskii,a Galina A. Gazievaa and Yulia V. Nelyubinab
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian
Federation. Fax:+7 499 135 5328; e-mail: kani@server.ioc.ac.ru
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax:+7 499 135 5085; e-mail: unelya@xrlab.ineos.ac.ru
DOI: 10.1016/j.mencom.2015.11.027
Condensation of 4,6-di(tert-butyl)-3-nitro-1,2-benzoquinone with 1,3-dimethyl-3a,9a-diphenyl-3,3a,9,9a-tetrahydroimidazo[4,5-e]-
thiazolo[3,2-b][1,2,4]triazine-2,7(1H,6H)-dione inAcOH gives a new 6-(benzofuranylidene)tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-
[1,2,4]triazine-2,7-dione derivative, whose structure was confirmed by X-ray diffraction analysis.
But
The reactivity of 1,2-benzoquinone derivatives is being studied
incessantly.1–4 Their reactions with active methylene heterocyclic
compounds can proceed by various pathways depending on the
reactant structure.1 In many cases, multistage reactions involving
1,2-benzoquinones begin with aldol condensation, then its
products undergo subsequent transformations, probably due to
their instability. We have recently found that 3,5-di(tert-butyl)-
1,2-benzoquinone 1 can undergo aldol condensation with
[(imidazotriazin-3-yl)thio]acetic acid 2 and imidazothiazolo-
triazinedione 3 to give two isomers 4 and 5 (Scheme 1).4 Com-
pounds 2 and 3 undergo similar reactions with N-substituted
isatins.5,6
Me
N
O
H
N
Ph
O
O
N
+
O
But
N
S
N
Ph
NO2
Me
3
6
But
NO2
OH
Me
N
O
H
N
Ph
i
N
O
O
N
S
N
Ph
O
Me
Me
N
Ph
O
Me
N
H
N
Ph
Ph
7
H
N
N
N
O
Scheme 2 Reagents and conditions: i, AcOH, 22°C, 7 days.
O
S
N
N
S
COOH
N
N
H
Ph
acetate–hexane, 1:2). The compound with Rf = 0.25 was isolated
and its structure was determined based on X-ray diffraction (XRD)
data. Unexpectedly, it turned out to be a hitherto unknown poly-
heterocyclic compound 7 which contained imidazolidine, triazine,
thiazolidine and benzofuranylidene moieties (see Scheme 2).† The
best conditions for the synthesis of compound 7 in an optimum
yield of 47% were as follows: keeping the reaction mixture in
glacial acetic acid for 7 days at 22°C.
Me
Me
2
3
But
O
But
O
1
Me
Ph
The presence of a furanylidene moiety in the product molecule
was particularly unusual. Apparently, nitroquinone 6 does not
H
N
N
But
But
N
Me
O
Ph
Ph
H
N
O
N
N
N
N
S
1H NMR spectra were recorded on a Bruker AM-300 spectrometer
†
+
O
Ph
Me
O
S
N
(300.13 MHz) in DMSO-d6 (TMS as the internal standard). Melting
points were determined in a Sanyo GALLENKAMP instrument. A 1100
LC/MSD (Agilent Technologies, USA) LC-mass spectrometer equipped
with an ELSD PL-ELS-1000 mass detector and an Onyx monolithic
C18 column (50×4.6 mm) was used. The flow rate of the eluent was
3.75 ml min–1 [eluent A: acetonitrile–water (2.5:97.5) containing 0.1%
of trifluoroacetic acid; eluent B: acetonitrile–water (97.5:2.5) containing
0.1% of trifluoroacetic acid; elution mode gradient: 100% A (0 min) ®
100% B (4.2–4.6 min) ® 100% A (4.8 min)]. Compound 7, Rt = 4.37 min.
Tricycle 3 was prepared by the reaction of bromoacetic acid with
imidazotriazine 8 in glacial acetic acid.8 Imidazotriazine 8 was obtained by
a-ureidoalkylation of thiosemicarbazide with 1,3-dimethyl-4,5-dihydroxy-
4,5-diphenylimidazolidin-2-one,9 which in turn was synthesized by the
reaction of 1,2-dioxo-1,2-diphenylethane (benzil) with 1,3-dimethylurea.10
4,6-Di(tert-butyl)-3-nitro-1,2-benzoquinone 6 was obtained by treatment
of 2,4,6-tri(tert-butyl)phenol with 60% nitric acid.11
N
O
O
Me
But
4
5
But
Scheme 1
Here, we report on the reaction of tricycle 3 with 3,5-di(tert-
butyl)-3-nitro-1,2-benzoquinone 6 following the unusual path-
way, which results in a new polyheterocyclic compound 7 as the
main product (Scheme 2).
The reaction of nitroquinone 6 with tricyclic compound 3 was
studied under various conditions: glacial acetic acid as the solvent,
reaction time from 30 min to 7 days, reaction temperature from
22 to 70°C. Reaction progress was followed by TLC (ethyl
© 2015 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2015, 25, 476–478
But
But
But
HO
O
HO
O
Me
N
Me
N
Me
N
O
OH
O
S
HO
H
H
N
Ph H
N
H
N
Ph
Ph
Ph
Ph
N
N
N
O
O
But
O
But
But
3 + 6
O
N
S
N
S
N
N
N
NO2
N
H
NO2
NO2
Ph
Me
Me
Me
A
B
C
But
But
Me
Me
N
H
N
H
N
Ph
Ph
HO
1
HO
O
O
O
N
N
N
O
O
2
Me
N
But
But
N
S
N
S
Ph H
N
N
H
N
O
H
S
Ph
Ph
H
Me
NH
Me
NO2
NO2
O
H
D
D
N
S
N
Ph H
O
Me
Me
O
N
8
N
N
Ph
Ph
Me
HN
But
O
N
NH
N
Ph
N
Me
But
N
O
Ph
N
Me
O
3
S
H
NO2
2
O
But
But
1
O
HO
ButO
O
+
7
But
HO
But
NO2
NO2
E
9
Scheme 3
react with tricyclic compound 3 to give products of aldol con-
densation, in contrast to the reaction with quinone 1, due to
steric factors (the nitro group is in the carbonyl plane). It seems
likely that the nitroquinone is involved in cascade process initiated
by nucleophilic 1,4-addition of active methylene compound 3 to
benzoquinone system to afford intermediate A (Scheme 3). The
mechanism of benzodioxin D formation involves opening of
the thiazolidine ring (A ® C). The further transformation of D
is possible by the ‘concerted’ mechanism. The reaction of dioxin
adduct D with the second tricyclic molecule 3 can result in the
dioxin ring opening with elimination of imidazotriazine 8 to give
ester E. An example of dioxin ring opening with C-nucleophiles
was described in detail previously.7 Intramolecular condensa-
tion E ® 7 occurs with oxidation and de-tert-butylation, which
involves a second molecule of nitro-1,2-benzoquinone 6. The
tert-butyl ether of pyrocatechol 9 was not detected in the reaction
mixture. However, similar intramolecular condensations involving
de-tert-butylation were discussed in literature.1(b)
Single crystals of compound 7 for XRD were grown from
isopropyl alcohol resulting in a 1:1 crystallosolvate 7. According
to XRD data (Figure 1),‡ the imidazolidine and triazine cycles
in 7 adopt an envelope conformation with the C(3) and N(2)
atoms deviating by 0.39(1) and 0.50(1) Å, respectively; the other
heterocycles are planar within 0.02(1) Å. The planarity of the
central fragment is apparently also governed by a C(27)–H···O(2)
[H···O 2.20(1) Å, ÐCHO 134(1)°] intramolecular bond and a
O(3)···S(1) contact [O···S 2.728(3)Å]. The latter may be rationalized
as a charge transfer from a lone electron pair of the oxygen atom
O(3) to the s*-orbital of the S(1)–C(4) bond, as judged by the
O(3)S(1)C(4) [167.15(2)°] angle being close to linear.
In a crystal, the molecules of 7 form homochiral chains
through an N(2)–H···O(1) hydrogen bond [N···O 2.846(3) Å,
ÐNHO 137(1)°]; however, the resulting crystal structure is centro-
6-[5-tert-Butyl-7-hydroxy-6-nitro-2-oxo-1-benzofuran-3(2H)-ylidene]-
1,3-dimethyl-3a,9a-diphenyl-3,3a,9,9a-tetrahydroimidazo[4,5-e]thiazolo-
[3,2-b][1,2,4]triazine-2,7(1H,6H)-dione 7. A mixture of 4,6-di(tert-butyl)-
3-nitro-1,2-benzoquinone 6 (1.25 g, 5 mmol) and tricycle 3 (1.96 g,
5 mmol) in AcOH (25 ml) was stirred for seven days at 22°C. The minor
precipitate of the original compound 3 was filtered off and washed with
glacial acetic acid. The filtrate was diluted with cold water (275 ml). The
oily precipitate was successively extracted with equal volumes of dichloro-
methane (3×50 ml) and ethyl acetate (3×50 ml). The extracts were washed
with a sodium carbonate solution (3×50 ml) and water (3×50 ml) in a
separating funnel and kept for 3–4 h over anhydrous Na2SO4. The dry
solutions were combined and concentrated to a minimum volume to give
1.5 g of compound 7, yield 47%, yellow crystals, mp 293–295°C (ethyl
acetate–hexane, 1:2). 1H NMR, d: 1.32 (s, 9H, But), 2.62 (s, 3H, MeN),
2.69 (s, 3H, MeN), 6.71–7.24 (m, 10H, 2Ph), 8.07 (s, 1H, NH), 8.78 (s,
1H, C4H), 11.67 (s, 1H, OH). 13C NMR, d: 25.52, 25.57 (NMe), 30.60
(Me3C), 35.66 (Me3C), 79.79, 82.28 (CPh), 116.85, 120.69, 122.85, 126.36,
127.51, 127.66, 128.06, 128.12, 128.41, 133.72, 134.41, 136.32, 140.84,
143.15, 147.31, 158.92, 159.18, 167.17 (C=O). MS, m/z: 641.2 [M+H]+,
642.1 [M+2H]+ (Calc. for C32H28N6SO7, m/z: 641.1818 [M+H]+).
‡
Crystallographic data for 7. The crystals of 7 (C38H44N6O9S, M =
= 760.85) are monoclinic, space group P21/n, at 10 K: a = 11.3193(14),
b = 14.0131(17) and c = 24.123(3) Å, b = 96.620(3)°, V = 3800.8(8) Å3,
Z = 1, dcalc = 1.330 g cm–3, m(MoKa) = 1.48 cm–1, F(000) = 1608. The
intensities of 28252 reflections were measured with a Bruker SMART
1000 CCD diffractometer [l(MoKa) = 0.71072 Å, w-scans, 2q < 54°],
and 8277 independent reflections (Rint = 0.1011) were used in further
refinement. The structure was solved by the direct method and refined
by the full-matrix least-squares technique against F2 in the anisotropic-
isotropic approximation. The hydrogen atoms of OH and NH groups
were found in difference Fourier synthesis; the H(C) atom positions were
calculated. All hydrogen atoms were refined in the isotropic approxima-
tion within the riding model. The refinement converged to wR2 = 0.1064
and GOF = 1.008 for all the independent reflections [R1 = 0.0533 was
calculated against F for 4020 observed reflections with I > 2s(I)]. All
calculations were performed using SHELXTL PLUS.12
CCDC 1061751 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via http://www.ccdc.cam.ac.uk.
– 477 –

Mendeleev Commun., 2015, 25, 476–478
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C(2)
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C(22)
C(28)
C(21)
C(5)
C(23)
C(24)
N(1)
S(1)
C(20)
C(25)
N(4)
C(3)
C(12)
C(19)
N(3)
N(2)
C(26)
C(30)
C(4)
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C(27)
C(32)
C(13) C(14)
O(2)
O(7)
C(29)
C(15)
C(11)
C(18)
C(31)
C(8)
C(17)
C(16)
C(10)
C(9)
Figure 1 General view of heterocycle 7 in representation of atoms via
thermal ellipsoids (p = 50%). Hydrogen atoms, except those of NH and OH
groups and the H(C) atom involved in an intramolecular hydrogen bond, are
omitted for clarity.
symmetric (space group P21/n) owing to hydrogen bonding with
two isopropyl alcohol molecules [O···O 2.554(3) and 2.815(3) Å,
ÐNHO 147(1) and 145(1)°] and between them [O···O 2.715(3) Å,
ÐNHO 162(1)°]. It assembles neighboring molecules of 7 into
centrosymmetric dimers in such a manner that their benzofuran
moieties face each other (the shortest C···C distance is ca. 3.7 Å).
These dimers, which link neighboring homochiral H-bonded
chains, seem to be additionally stabilized by a short O(6)···S(1)
contact [O···S 3.162(3) Å]; in this case, charge transfer occurs
from a lone electron pair of the S(1) sulfur atom to the s*-orbital
of the O(6)–N(6) bond [ÐSON 132.26(2)°].
In conclusion, we were the first to study the condensation of
tricycle 3 with 3,5-di(tert-butyl)-3-nitro-1,2-benzoquinone to obtain
a new polyheterocyclic compound, 6-[5-tert-butyl-7-hydroxy-
6-nitro-2-oxo-1-benzofuran-3(2H)-ylidene]-1,3-dimethyl-3a,9a-
diphenyl-3,3a,9,9a-tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-
[1,2,4]triazine-2,7(1H,6H)-dione. The mechanism of its cascade
formation process initiated by nucleophile 1,4-addition has been
suggested.
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We are grateful to Dr. Yu. A. Sayapin (Research Institute of
Physical and Organic Chemistry, Southern Federal University,
Rostov-on-Don) for the fruitful discussions on the subject of this
publication.
This study was supported by the Russian Foundation for
Basic Research (project no. 14-03-31729).
Received: 29th April 2015; Com. 15/4613
– 478 –