4H-Thiopyrans bearing a mesoionic ring

Article abstract of DOI:10.1016/j.mencom.2009.11.008

The preparation of 4-(2,6-diamino-4H-thiopyran-3,5-dicarbonitrile) derivatives of sydnone and sydnone imines based on the ternary condensation of 4-formyl sydnones and sydnone imines with malononitrile and 2-cyanothioacetamide is reported.

Full text of DOI:10.1016/j.mencom.2009.11.008

Mendeleev
Communications
Mendeleev Commun., 2009, 19, 320–321
4H-Thiopyrans bearing a mesoionic ring
Ilya A. Cherepanov, Evgeny D. Savin, Natal’ya G. Frolova, Maria O. Shishkova,
Ivan A. Godovikov, Kyrill Yu. Suponitsky, Konstantin A. Lyssenko and Valery N. Kalinin*
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 6549; e-mail: vkalin@ineos.ac.ru
DOI: 10.1016/j.mencom.2009.11.008
The preparation of 4-(2,6-diamino-4H-thiopyran-3,5-dicarbonitrile) derivatives of sydnone and sydnone imines based on the
ternary condensation of 4-formyl sydnones and sydnone imines with malononitrile and 2-cyanothioacetamide is reported.
Sydnones (1,2,3-oxadiazolium-5-olates) and their nitrogen ana-
logues, sydnone imines (1,2,3-oxadiazolium-5-amidines), are the
mostly investigated representatives of mesoionic heterocyclics
and associated with a number of biological activities.1–3 Alde-
hyde functionality at the C(4)-position of these mesoionic hetero-
cycles opens wide perspectives for the construction of numerous
promising physiologically active compounds.
Multicomponent condensations involving aryl or heteroaryl
carboxaldehydes and malononitrile are widely used in hetero-
cyclic synthesis.4,5 However, recent attempts to apply the meth-
odology to 4-formylsydnones 1 failed.6 We were the first to
discover that the ternary condensation of 3-substituted 4-formyl-
sydnones with malononitrile and 2-cyanothioacetamide affords
2,6-diamino-4-(1,2,3-oxadiazolium-5-olate-4-yl)-4H-thiopyran-
3,5-dicarbonitriles 2 in good yields (Scheme 1).
H2N
S
NC
Pri
NH2
Pri
CHO
i
N
N
CN
N
N
N
O
N
O
O
Ph
Ph
O
4
5 40%
Scheme 3 Reagents and conditions: i, malononitrile (1.0 equiv.), 2-cyano-
thioacetamide (1.0 equiv.), Et3N cat., isopropanol, reflux, 0.5 h.
followed by hydrolysis resulted in the corresponding 4-formyl
derivatives of sydnone imine 4 in excellent yields (Scheme 2).
We also applied this method to the syntheses of 4-formyl
derivatives of sydnones. Thus, for instance, 4-formyl-3-methyl-
sydnone has been obtained in 80% yield by this procedure,
while the typical Vilsmeier reaction gives only a 34% yield of
the target compound.8
The condensation of 4-formylsydnone imine 4 with malono-
nitrile and 2-cyanothioacetamide also leads to 4H-thiopyran
derivative 5 (Scheme 3). At the same time, the Knoevenagel
condensation of 4 with malononitrile almost quantitatively yields
methylenemalononitrile derivative 6 (Scheme 4). Compound 6
is an intermediate in the synthesis of thiopyran 5: a treatment
of 6 with 2-cyanothioacetamide also furnished 5 in 93% yield.
The structure of 6 was confirmed by X-ray diffraction analysis
(Figure 1).† The bond length distribution in 6 is close to expected
one for mesoionic molecules.9 Due to steric repulsion, the dicyano-
ethylene moiety is turned off the plane of the mesoionic ring
with the torsion angle C(5)C(4)C(15)C(16) of 25.5°. The bond
lengths in dicyanoethylene fragment is almost indentical to those
observed in phenylmethylidenemalononitrile.10 Thus, we may
conclude that the electron-acceptor characteristics of mesoionic
cycle are comparable with those of benzene.
H2N
S
NC
NH2
R
R
CHO
O
i
N
N
CN
N
N
O
O
O
R = Me 65%
R = Ph 78%
1
2
Scheme 1 Reagents and conditions: i, malononitrile (1.0 equiv.), 2-cyano-
thioacetamide (1.0 equiv.), Et3N cat., isopropanol, reflux, 0.5 h.
4-Formylsydnone imines were hitherto unknown. Our attempts
to prepare these compounds by the Vilsmeier formylation of
sydnone imines or by the reaction of 4-lithio derivatives of sydnone
imines7 with DMF were unsuccessful. However, we found that
the interaction of 4-lithio-3-isopropyl-N6-benzoylsydnone imine
3 with 1-methoxy-N,N-dimethylmethanaminium methyl sulfate
Pri
Pri
H
Li
O
O
N
i
N
The same steric reasons lead to the rather unusual disposition
of carbonyl group, which is oriented towards O(1) atom, in
Ph
Ph
N
N
N
N
O
O
CN
CN
3
Pri
Pri
CHO
N
i
N
O
4
ii, iii
N
N
N
O
O
N
Ph
Ph
O
4 91%
6 95%
Scheme 2 Reagents and conditions: i, BuLi (1.1 equiv.), THF, –85 °C,
0.5 h; ii, 1-methoxy-N,N-dimethylmethanaminium methyl sulfate (1.2 equiv.),
THF, –85 °C to room temperature; iii, H2O.
Scheme 4 Reagents and conditions: i, malononitrile (1.0 equiv.), DMAP,
AcOH cat., isopropanol, reflux, 0.5 h.
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© 2009 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2009, 19, 320–321
above contact corresponds to bonding interaction – the critical
O(8)
O(1)
N(2)
N(3)
C(10)
point (3, –1) was located in the interatomic area. Based on the
Espinosa correlation scheme,15 the energy of this contact was found
to be 3.7 kcal mol–1. Therefore, the molecular structure of 6 is
mostly governed by intra- rather than intermolecular interactions.
Taking into account relatively high decomposition tempera-
ture of 6, this compound can represent a promising material
for potential applications in optoelectronics.16 Therefore, we
have estimated its molecular hyperpolarizability (b) at the same
level of sophistication as for geometry optimization, which was
shown to be accurate enough for calculation of molecular
nonlinear optical (NLO) properties.17,18 Hyperpolarizability of
6 was estimated by the finite field method as implemented in
the Gaussian program (keyword Polar=EnOnly) and presented
in a vectorial form according to the expression
C(23)
C(21)
C(11)
C(12)
C(13)
C(7)
C(9)
C(5)
N(6)
C(4)
C(22)
C(14)
C(15)
C(17)
C(16) N(18)
C(19)
N(20)
Figure 1 General view of 6 in representation of atoms by thermal
ellipsoids (p = 50%). Selected bond lengths (Å): O(1)–N(2) 1.375(2),
O(1)–C(5) 1.394(2), N(2)–N(3) 1.293(2), N(3)–C(4) 1.366(2), N(3)–C(21)
1.502(2), C(4)–C(5) 1.416(2), C(4)–C(15) 1.421(2), C(5)–N(6) 1.287(2),
N(6)–C(7) 1.391(2), C(7)–O(8) 1.221(2), C(7)–C(9) 1.498(2), C(15)–C(16)
1.352(2).
3
1
bvect
=
(bx2 + by2 + b2z), bj =
(bjii + biji + biij), i, j = x, y, z.
3 Σ
i = 1
contrast to acetylsydnone imine picrate11 and N-ethoxycarbonyl-
3-morpholinosydnone imine dihydrate,12 in which the trans
disposition of O(1) and O(8) atoms is observed. Such a mutual
disposition of the carbonyl group and mesoionic cycle leads to
the occurrence of the shortened contact O(1)···O(8) with the
interatomic separation of 2.629(1) Å.
The value of b is 934 a.u. and comparable to that of well-known
NLO-active compound dicyanovinylanisole (DIVA), which is
1245 a.u. obtained at the same level of theory.
Online Supplementary Materials
In addition to steric repulsion, the conformation of 6 can also
be a result of crystal packing effects. Indeed, in a crystal of 6,
one of the CN groups participates in the shortened so-called
N···π interactions with the mesoionic cycle (see Figure 2). The
interaction of this type, rather common for the mesoionic cycle,
was also observed in acetonitrile solvate of N6-acetyl-3-dimethyl-
amino-4-diphenylphosphinosidnonimine palladium dichloride.9
In order to analyze the nature of the above shortened con-
tact O(1)···O(7), we optimized the geometry of 6 at M052X/
6-311++G(d,p) level of theory using the Gaussian03 program.13
The geometry of the molecule in the crystal and the gas phase is
rather close. In particular, the torsion angle C(5)C(4)C(15)C(16)
equal to 29.1 and O(1)···O(8) interatomic distances (2.632 Å)
are almost the same. The topological analysis of the electron
density function [r(r)] with the Bader’s ‘Atom in Molecule’
theory14 in the isolated molecule of 6 has revealed that the
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2009.11.008.
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O(8)
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†
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For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2009.
2009, DOI:10.1021/jp902293q.
Received: 8th June 2009; Com. 09/3346
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