2-Amino-4-(2-methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H- chromene-3-carbonitrile and 2-amino-4-(2-methoxyphenyl)-7,7-dimethyl-3-nitro-4, 6,7,8-tetrahydro-5H-chromen-5-one hemihydrate

Article abstract of DOI:10.1107/S0108270105037078

Calculations of the conformational preferences of the methoxyphenyl substituent with respect to the pyran ring have been carried out for the two title compounds, C₁₉H₂₀N₂O₃, (II), and C₁₈H₂₀

Full text of DOI:10.1107/S0108270105037078

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
inskaia, 2001; Nesterov et al., 2004; Nesterova et al., 2004).
Some 4H-pyran derivatives are potential bioactive compounds
and can be used as calcium antagonists (Suarez et al., 2002).
Such heterocyclic compounds have structures similar to those
of the well known 1,4-dihydropyridines (Triggle et al., 1980;
Bossert et al., 1981, 1989; Kokubun & Reuter, 1984), which
exhibit high bioactivities. Thus, there has been a growing
interest in the structures of 4H-pyran derivatives (Florencio &
Garcia-Blanco, 1987; Bellanato et al., 1988; Lokaj et al., 1990;
Marco et al., 1993; Suarez et al., 2002).
ISSN 0108-2701
2-Amino-4-(2-methoxyphenyl)-7,7-
dimethyl-5-oxo-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile and
2-amino-4-(2-methoxyphenyl)-7,7-
dimethyl-3-nitro-4,6,7,8-tetrahydro-
5H-chromen-5-one hemihydrate
Vladimir N. Nesterov,a* Victor P. Kislyi,b Joseph L.
Sabutis,a Volodymyr V. Nesterov,c David J. Wiedenfelda
and Victor V. Semenovb
aDepartment of Natural Sciences, New Mexico Highlands University, Las Vegas,
NM 87701, USA, bInstitute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky Prosp., Moscow, Russian Federation, and cDepartment of Chemistry
and Biochemistry, The University of Texas at Austin, TX 78712-0165, USA
Correspondence e-mail: vnesterov@nmhu.edu
Received 26 October 2005
Accepted 10 November 2005
Online 30 November 2005
Syntheses and X-ray structural investigations have been
carried out for compounds (II) and (III) (Figs. 1 and 2). Most
of the geometric parameters are very similar to the standard
values (Allen et al., 1987) and very close to our and literature
data for similar 4H-pyran derivatives (Kislyi et al., 1999;
Suarez et al., 2002; Nesterov et al., 2004).
The X-ray analyses show that the molecules of (II) and (III)
have slightly different conformations. The pyran ring in both
structures adopts a ¯attened boat conformation, with a
deviation of atoms O1 and C4 from the C2/C3/C5/C10 plane
Calculations of the conformational preferences of the
methoxyphenyl substituent with respect to the pyran ring
have been carried out for the two title compounds,
C19H20N2O3, (II), and C18H20N2O5Á0.5H2O, (III). In both
molecules, the heterocyclic ring adopts a ¯attened boat
conformation and the fused cyclohexenone ring adopts a
`sofa' conformation. The dihedral angles between these two
¯at fragments are 14.5 (1) and 9.3 (1)ꢀ in (II) and (III),
respectively. In both molecules, the methoxy group of the
pseudo-axial aryl substituent is syn with respect to the pyran
ring. The dihedral angles between the 2-methoxyphenyl rings
and the ¯at parts of the pyran rings are 86.3 (1) and 87.0 (1)ꢀ,
respectively. In the crystal structure of (II), intermolecular
NÐHÁ Á ÁN and NÐHÁ Á ÁO hydrogen bonds link molecules into
a three-dimensional framework. In the crystal structure of
(III), a strong intramolecular NÐHÁ Á ÁO hydrogen bond links
the ¯at conjugated HÐNÐC CÐNÐO fragment into a six-
membered ring. In (III), the water molecule lies on a twofold
axis and forms bifurcated OÐHÁ Á ÁO hydrogen bonds with the
NO2 group of the molecule. Also in (III), hydrogen bonds link
the organic and water molecules into in®nite tapes along the
c axis.
Ê
[planar within 0.008 (2) and 0.001 (2) A] of 0.151 (2) and
Ê
0.203 (2) A in (II), and 0.108 (2) and 0.218 (2) A in (III),
Ê
Comment
The present investigation is a continuation of our systematic
work that includes the syntheses and structural studies of
unsaturated nitriles as potential non-linear optical materials
(Nesterov et al., 2000, 2001a,b) and heterocyclic compounds
that may be obtained using such nitriles (Nesterov & Viltch-
Figure 1
A view of (II), showing the atom numbering used. The non-H atoms are
shown with displacement ellipsoids drawn at the 50% probability level.
Acta Cryst. (2005). C61, o741±o744
DOI: 10.1107/S0108270105037078
# 2005 International Union of Crystallography o741

organic compounds
respectively. The bending of the ring along the lines O1Á Á ÁC4,
C2Á Á ÁC10 and C3Á Á ÁC5 is, respectively, equal to 16.6 (2),
12.4 (2) and 13.2 (2)ꢀ in (II), and 15.2 (2), 9.0 (2) and 14.5 (2)ꢀ
in (III). According to our previous work and literature data,
the pyran ring is ¯exible but usually adopts a ¯attened boat
conformation. In both molecules, the fused cyclohexenone
ring adopts a sofa conformation; atom C8 deviates from the
C7/C6/C5/C10/C9 plane [planar within 0.030 (1) and
1987). Variations of the other bond lengths in the ¯at frag-
ments are less distinct in (II). However, in (III), the C3ÐN2
distance is considerably shorter than usual for CÐNO2 bonds
Ê
(1.468 A; Allen et al., 1987) and the N2ÐO4 distance is
distinctly longer than the standard value (Allen et al., 1987).
In the crystal structure of (II), both H atoms of the NH2
group participate in intermolecular NÐHÁ Á ÁN and NÐHÁ Á ÁO
hydrogen bonds that link the molecules into a three-dimen-
sional framework (Fig. 3 and Table 2). In (III), a strong
intramolecular NÐHÁ Á ÁO hydrogen bond links the ¯at
Ê
Ê
0.024 (1) A] by 0.636 (1) and 0.666 (2) A for (II) and (III),
respectively. The dihedral angles between these two ¯at
fragments are 14.5 (1) and 9.3 (1)ꢀ in (II) and (III), respec-
tively. In both molecules, the methoxy substituent of the aryl
group is anti relative to the H atom bonded to C4 [H4AÐC4Ð
C13ÐC14 = 167 and 178ꢀ, and C4ÐC13ÐC14ÐO3 = 1.9 (2)
and 2.1 (3)ꢀ]. The phenyl substituents occupy pseudo-axial
positions and form dihedral angles with the ¯at moieties of the
pyran rings of 86.3 (1) and 87.0 (1)ꢀ in (II) and (III), respec-
tively. Such mutual orientation of these fragments and the
¯atness of the heterocyclic rings leads to OÁ Á ÁC intramolecular
conjugated HÐNÐC CÐNÐO fragment into
a six-
membered ring. The water molecule lies on a twofold axis and
forms bifurcated OÐHÁ Á ÁO hydrogen bonds with the NO2
group of the molecule. In the crystal structure, hydrogen
bonds link the organic and water molecules into in®nite tapes
along the c axis (Fig. 4 and Table 4).
Analysis of the crystal packing shows that in (III) there is
=
only one intermolecular steric contact [O4Á Á ÁO4iii
Ê
2.894 (2) A; symmetry code: (iii) x, y + 2, z], which is
equal to the sum of the van der Waals radii of the O atoms
(Rowland & Taylor, 1996). The other geometric parameters in
(II) and (III) have standard values (Allen et al., 1987).
Ê
steric interactions [O3Á Á ÁC5 = 2.911 (3) A and O3Á Á ÁC10 =
Ê
Ê
Ê
Ê
3.109 (3) A in (II), and O3Á Á ÁC2 = 3.074 (3) A, O3Á Á ÁC3 =
Ê
3.006 (3) A, O3Á Á ÁC5
=
2.969 (3) A and O3Á Á ÁC10
=
3.018 (3) A in (III)]. These distances are shorter than the sum
of the van der Waals radii of O and C (Rowland & Taylor,
1996), especially in the case of (II). Such steric hindrance
causes elongation of the C4ÐC13 bond lengths to 1.525 (2)
Using computational methods (GAUSSIAN03; Frisch et al.,
2003), we explored the conformational preferences of the
methoxyphenyl substituent with respect to the pyran ring in
molecules (II) and (III). This was performed ®rst at the AM1
level by minimizing the conformer found in the crystal and
then rotating the H4ÐC4ÐC13ÐC14 angle by 10ꢀ increments
and minimizing the conformations encountered until the
original conformer was generated once again. For the mol-
ecules of both (II) and (III), two minima were found. The ®rst
has the methoxy substituent on the benzene ring syn to the
pyran ring (H4ÐC4ÐC13ÐC14 angle close to 180ꢀ), similar
Ê
and 1.527 (3) A, respectively, in comparison with neighboring
Csp3ÐCsp2 distances that are equal to standard values (Allen
et al., 1987).
As was described previously for related compounds (Kislyi
et al., 1999; Nesterov et al., 2001, 2004; Nesterova et al., 2004),
there is conjugation [especially in (III)] between the donor
(NH2) and acceptor [CN in (II) and NO2 in (III)] groups via
the C2 C3 double bond (Tables 1 and 3). Thus, in both
molecules, the C2ÐN1 distances are shorter than the average
Ê
conjugated CÐN single bond (1.370 A) found in the
Cambridge Structural Database (Allen, 2002). In contrast, the
C2 C3 bond lengths are elongated in comparison with the
C5 C10 bond length and the standard value (Allen et al.,
Figure 2
A view of (III), showing the atom numbering used. The non-H atoms are
shown with displacement ellipsoids drawn at the 50% probability level.
Dashed lines indicate the intramolecular NÐHÁ Á ÁO hydrogen bond and
the OÐHÁ Á ÁO bifurcated hydrogen bonds.
Figure 3
A projection of the crystal packing of (II) along the a axis. [Symmetry
1
1
1
codes: (i) x + 1, y + 1, z + 1; (ii) x + , y + , z + .]
2
2
2
ꢁ
o742 Nesterov et al. C19H20N2O3 and C18H20N2O5Á0.5H2O
Acta Cryst. (2005). C61, o741±o744

organic compounds
yield 71% for (III)]. Both compounds were characterized by 1H and
13C NMR spectroscopy. The crystals were grown by slow isothermic
evaporation of a solution in acetonitrile for (II) and ethanol for (III).
Compound (II)
Crystal data
3
C19H20N2O3
Mr = 324.37
Monoclinic, P21=n
Ê
a = 8.7941 (18) A
Dx = 1.289 Mg m
Mo Kꢁ radiation
Cell parameters from 24
re¯ections
ꢂ = 11±12ꢀ
ꢃ = 0.09 mm
T = 153 (2) K
Ê
Ê
b = 17.450 (4) A
1
c = 11.007 (2) A
ꢀ = 98.174 (16)ꢀ
3
Ê
V = 1671.9 (6) A
Z = 4
Prism, colorless
0.45 Â 0.30 Â 0.25 mm
Data collection
Siemens P3/PC diffractometer
!/2ꢂ scans
h = 0 ! 10
k = 0 ! 20
3105 measured re¯ections
2907 independent re¯ections
2562 re¯ections with I > 2ꢄ(I)
Rint = 0.027
l = 13 ! 12
3 standard re¯ections
every 97 re¯ections
intensity decay: 3%
ꢂ
max = 25.0ꢀ
Re®nement
Figure 4
A projection of the crystal packing of (III) along the b axis. [Symmetry
code: (iii) x, y + 2, z.]
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.036
wR(F2) = 0.094
S = 1.04
2907 re¯ections
w = 1/[ꢄ2(F2o) + (0.05P)2
+ 0.54P]
where P = (F2o + 2Fc2)/3
(Á/ꢄ)max < 0.001
3
Ê
Áꢅmax = 0.22 e A
to the con®guration observed in the crystal structures (Figs. 1
and 2). The second has the methoxy substituent on the
benzene ring anti to the pyran ring (H4ÐC4ÐC13ÐC14 angle
close to 0ꢀ). For compound (II) at the AM1 level, the anti
3
Ê
0.20 e A
220 parameters
H-atom parameters constrained
Áꢅmin
=
Table 1
Selected geometric parameters (A, ) for (II).
ꢀ
Ê
conformation is predicted to be the global minimum, being
1
O1ÐC2
O1ÐC10
O2ÐC6
N1ÐC2
N2ÐC1
1.3749 (15)
1.3773 (16)
1.2232 (16)
1.3317 (17)
1.1514 (17)
C1ÐC3
C2ÐC3
C4ÐC13
C5ÐC10
C5ÐC6
1.4162 (18)
1.3535 (18)
1.5246 (18)
1.3299 (18)
1.4679 (18)
1.8 kcal mol
more stable than the syn minimum and
1
6.4 kcal mol more stable than the highest energy confor-
mation. A frequency calculation con®rmed that the highest
energy conformation corresponds to an energy maximum. In
contrast, higher level restricted Hartree±Fock calculations on
the two minima of (II) [basis set 6-311++G(d,p)] predict that
the syn conformer observed in the crystal is more stable than
the anti conformer by 0.9 kcal mol 1. AM1 calculations on
(III) gave similar results, with the anti conformer predicted to
C2ÐO1ÐC10
C14ÐO3ÐC19
118.38 (10)
117.19 (11)
N2ÐC1ÐC3
177.83 (14)
C19ÐO3ÐC14ÐC15
15.06 (19)
1
be more stable than the syn by 0.5 kcal mol and also more
1
Table 2
Hydrogen-bond geometry (A, ) for (II).
ꢀ
Ê
stable than the highest energy conformation by 5.1 kcal mol
.
A frequency calculation con®rmed that the highest energy
conformation corresponds to an energy maximum. Similar to
the results with (II), the higher level ab initio calculations
(same basis set used) predict the conformer observed in the
crystal of (III) to be the minimum energy conformer: the syn
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N1ÐH1AÁ Á ÁN2i
0.88
0.88
2.18
2.07
3.041 (2)
2.943 (2)
166
173
N1ÐH1BÁ Á ÁO2ii
Symmetry codes: (i) x ‡ 1; y ‡ 1; z ‡ 1; (ii) x ‡ 12; y ‡ 21; z ‡ 21.
1
conformer is predicted to be 2.2 kcal mol more stable than
the anti.
Compound (III)
Crystal data
Experimental
3
C18H20N2O5Á0.5H2O
Dx = 1.309 Mg m
Mo Kꢁ radiation
Cell parameters from 24
re¯ections
Compounds (II) and (III) were obtained by the reaction of
(2-methoxybenzylidene)malononitrile, (Ia), or trans-1-cyano-2-(2-
methoxyphenyl)-1-nitroethylene, (Ib), with 5,5-dimethylcyclohexane-
1,3-dione (dimedone) according to literature procedures (Kislyi et al.,
1999; Nesterov & Viltchinskaia, 2001). The precipitates were isolated
and recrystallized from acetonitrile for (II) and from ethanol for (III)
[m.p. 474 K and yield 96% for (II), and m.p. 435 K (hemihydrate) and
Mr = 353.37
Monoclinic, C2=c
Ê
a = 28.461 (5) A
ꢂ = 10±11ꢀ
ꢃ = 0.10 mm
T = 298 (2) K
Ê
b = 9.456 (2) A
1
Ê
c = 15.860 (3) A
ꢀ = 122.819 (11)ꢀ
3
Ê
V = 3587.1 (13) A
Z = 8
Prism, colorless
0.40 Â 0.35 Â 0.30 mm
ꢁ
Acta Cryst. (2005). C61, o741±o744
Nesterov et al.
C19H20N2O3 and C18H20N2O5Á0.5H2O o743

organic compounds
Data collection
program(s) used to solve structure: SHELXS97 (Sheldrick, 1990);
program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997);
molecular graphics: SHELXTL-Plus; software used to prepare
material for publication: SHELXL97.
Enraf±Nonius CAD-4
diffractometer
!/2ꢂ scans
3162 measured re¯ections
3097 independent re¯ections
1749 re¯ections with I > 2ꢄ(I)
Rint = 0.038
ꢂmax = 25.0ꢀ
h = 0 ! 33
k = 0 ! 11
l = 18 ! 15
3 standard re¯ections
every 97 re¯ections
intensity decay: 3%
The authors thank the NIH (grant No. 1 P20 MD001104-01,
National Center on Minority Health and Health Disparities)
for ®nancial support.
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.055
wR(F2) = 0.116
S = 1.05
3097 re¯ections
238 parameters
H atoms treated by a mixture of
independent and constrained
re®nement
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FG1879). Services for accessing these data are
described at the back of the journal.
w = 1/[ꢄ2(F2o) + (0.0534P)2]
where P = (F2o + 2Fc2)/3
(Á/ꢄ)max < 0.001
3
Ê
Áꢅmax = 0.13 e A
References
3
Ê
0.16 e A
Áꢅmin
=
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ꢀ
Ê
O1ÐC2
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O2ÐC6
O4ÐN2
O5ÐN2
N1ÐC2
1.357 (3)
1.391 (2)
1.215 (3)
1.262 (2)
1.248 (2)
1.309 (3)
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5.9 (4)
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Table 4
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ꢀ
Ê
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DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N1ÐH1BÁ Á ÁO4
0.86
0.86
0.86
0.99 (4)
0.99 (4)
2.01
2.28
2.50
1.99 (4)
2.55 (4)
2.602 (3)
3.052 (3)
3.115 (3)
2.980 (3)
3.216 (3)
125
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129
179 (5)
125 (5)
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N1ÐH1BÁ Á ÁO4iii
N1ÐH1AÁ Á ÁO1Wiii
O1WÐH1WÁ Á ÁO5
O1WÐH1WÁ Á ÁO4
Symmetry code: (iii) x; y ‡ 2; z.
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trically calculated positions and re®ned using a riding model, with
Ê
CÐH distances of 0.95 and 0.93 A in (II) in (III), respectively, for
Ê
aromatic H atoms, 0.98 and 0.96 A for methyl H atoms, 0.99 and
Ê
Ê
0.97 A for CH2 H atoms, 1.0 and 0.98 A for CH H atoms, and 0.88 and
Ê
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È
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ꢁ
o744 Nesterov et al. C19H20N2O3 and C18H20N2O5Á0.5H2O
Acta Cryst. (2005). C61, o741±o744