Synthesis and X-ray structural investigations of 2-amino-7-methyl-4-(1- naphthyl)-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile and 2-amino-4-(1- naphthyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile

Article abstract of DOI:10.1007/s10870-005-5174-y

Synthesis and X-ray structural investigations have been carried out for the two title compounds C₂₀H₁₄N₂O₃ (4) and C₂₃H₁₄N₂O₃·C ₂H₃N (5). Compound 4 crystallizes in the monoclinic space group P2₁/n, with a = 7.0542(5), b = 8.822(1), c = 24.833(2) A, β = 94.30(4)°, V = 1541.0(4) A³, and Z = 4. Compound 5 crystallizes with an acetonitrile solvent molecule in the monoclinic space group P2₁/n, with a = 11.075(1), b = 7.854(1), c = 22.703(2) A, β = 90.67(1)°, V = 1974.5(3) A³, and Z = 4. In both molecules, the 4H-pyran ring adopts a flattened-boat conformation. The naphthalene substituent occupies a pseudo-axial position and the dihedral angle with the flat part of the pyran ring is equal to 94.6(3) in 4 and 76.8(3)° in 5. The mutual orientation of these fragments and the flatness of the heterocyclic rings lead to H...H intramolecular steric interactions: H4A...H18A 1.98 A in 4 and 2.11 A in 5. In the crystal of 4, intermolecular hydrogen bonds N-H...O and C-H...N link molecules into infinite tapes along the b axis. In the crystals of 5, intermolecular hydrogen bonds N-H...O and C-H...N link molecules into infinite layers parallel to the bc plane. In each case, the C-H...N interaction can be considered to be a weak hydrogen bond. The acetonitrile molecules link via intermolecular weak C-H...N hydrogen bonds to form infinite chains along the b axes.

Full text of DOI:10.1007/s10870-005-5174-y

Journal of Chemical Crystallography, Vol. 35, No. 11, November 2005 (ꢀC 2005)
DOI: 10.1007/s10870-005-5174-y
Synthesis and X-ray structural investigations
of 2-amino-7-methyl-4-(1-naphthyl)-5-oxo-
4H,5H-pyrano[4,3-b]pyran-3-carbonitrile
and 2-amino-4-(1-naphthyl)-5-oxo-4H,5H-
pyrano[3,2-c]chromene-3-carbonitrile
(1)∗
(1)∗
(1)
Vladimir N. Nesterov, David Wiedenfeld, Svitlana V. Nesterova,
(2)
and Lee M. Daniels
Received November 23, 2004; accepted April 12, 2005
Synthesis and X-ray structural investigations have been carried out for the two title
compounds C20H14N2O3 (4) and C23H14N2O3·C2H3N (5). Compound 4 crystallizes in
˚
the monoclinic space group P21/n, with a = 7.0542(5), b = 8.822(1), c = 24.833(2) A,
◦
˚ 3
β = 94.30(4) , V = 1541.0(4) A , and Z = 4. Compound 5 crystallizes with an acetonitrile
solvent molecule in the monoclinic space group P21/n, with a = 11.075(1), b = 7.854(1),
˚
◦
˚ 3
c = 22.703(2) A, β = 90.67(1) , V = 1974.5(3) A , and Z = 4. In both molecules, the
4
H-pyran ring adopts a flattened-boat conformation. The naphthalene substituent occupies
a pseudo-axial position and the dihedral angle with the flat part of the pyran ring is equal
◦
to 94.6(3) in 4 and 76.8(3) in 5. The mutual orientation of these fragments and the flatness
of the heterocyclic rings lead to H· · ·H intramolecular steric interactions: H4A· · ·H18A
˚
˚
---
1
.98 A in 4 and 2.11 A in 5. In the crystal of 4, intermolecular hydrogen bonds N H· · ·O
and C--- H· · ·N link molecules into infinite tapes along the b axis. In the crystals of 5, in-
termolecular hydrogen bonds N--- H· · ·O and C--- H· · ·N link molecules into infinite layers
parallel to the bc plane. In each case, the C--- H· · ·N interaction can be considered to be a
weak hydrogen bond. The acetonitrile molecules link via intermolecular weak C--- H· · ·N
hydrogen bonds to form infinite chains along the b axes.
KEY WORDS: α,β-Unsaturated nitriles; 4H-pyran; crystal structure; conjugation; intermolecular H-bonds.
pyran derivatives1–7 that can be obtained starting
Introduction
8,9
from different α,β-unsaturated nitriles. Some
H-pyran derivatives are potential bioactive com-
The present investigation is a continuation
of our work that includes synthesis and structural
studies of heterocyclic compounds, such as 4H-
4
10
pounds, such as adenosine receptor antagonists
and calcium antagonists.
11
(
1)
The investigated compounds were synthe-
sized by the reaction of (1-naphthylmethylene)
malononitrile 1 with 4-hydroxy-6-methyl-2-
pyrone 2 or 1 with 4-hydroxycoumarin 3 in ac-
Department of Natural Sciences, New Mexico Highlands Univer-
sity, Las Vegas, New Mexico 87701, USA.
Rigaku/MSC, Inc., 9009 New Trails Dr., The Woodlands, Texas
(2)
77381, USA.
∗
To whom correspondence should be addressed; e-mail:
vnesterov@nmhu.edu or dwiedenfeld@nmhu.edu.
6,7
cord with literature methods. We report here the
9
17
1
074-1542/05/1100-0917/0 ꢀC 2005 Springer Science+Business Media, Inc.

918
Nesterov, Wiedenfeld, Nesterova, and Daniels
Scheme 1.
synthesis of both 4H-pyran derivatives and their
full characterization by X-ray analysis (Scheme 1,
Figs. 1 and 2). The structures of these com-
pounds are not present in the Cambridge Struc-
g, 3.0 mmol) and 4-hydroxy-6-methyl-2-pyrone 2
(0.38 g, 3.0 mmol) or 1 (0.61 g, 3.0 mmol) and 4-
hydroxycoumarin 3 (0.49 g, 3.0 mmol), 20 mL of
ethanol and catalytic amounts of morpholine. The
mixtures were boiled while stirring for 1–3 min
and then allowed to cool. The precipitates were fil-
trated, washed with ethanol and then dried under
vacuum. After recrystallization from 1:1 acetoni-
trile/EtOH for 4 and from acetonitrile for 5, 88%
12
tural Database.
Experimental section
General methods for 4 and 5
(
0.88 g) and 85% (0.93 g) yields of pure products
A 50-mL round-bottom flask was charged
with (1-naphthylmethylene)malononitrile 1 (0.61
were obtained, respectively. The compounds had
melting points of 248 and 242 C, respectively.
◦
Fig. 2. View of the title molecule 5 and acetonitrile with
the atom-numbering scheme. The non-H atoms are shown
with thermal ellipsoids drawn at the 50% probability level.
H atoms are drawn as circles of arbitrary small radius for
clarity.
Fig. 1. View of the title molecule 4 with the atom-numbering
scheme. The non-H atoms are shown with thermal ellipsoids
drawn at the 50% probability level. H atoms are drawn as
circles of arbitrary small radius for clarity.

C H N O and C H N O ·C H N
919
20
14
2
3
23 14
2
3
2
3
1
14
The NMR for 4 follows: H (300 MHz,
using SHELXL97. In 5, the hydrogen atoms of
DMSO-d , δ): 8.35 (d, J = 7.4 Hz, 1H), 7.93
the CH group of the solvent acetonitrile molecule
6
3
(
dm, J = 7.4 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H),
were found from a difference Fourier map and
refined isotropically. All other H atoms in both
structures were placed in geometrically calculated
positions and introduced in the refinements us-
ing the riding approximation. The final difference
map showed no unusual features, with no signif-
icant peaks above the general background. The
crystal and structure determination data for 4 and
5 are summarized in Table 1.
7
.54 (m, 2H), 7.45 (t, J = 8.1 Hz, 1H), 7.23
(
d, J = 7.0 Hz, 1H), 7.13 (br s, 2H), 6.33 (d,
13
J = 1 Hz, 1H), 5.27 (s, 1H), 2.23 (s, 3H);
C
(75 MHz, DMSO-d , δ): 162.79, 161.35, 158.53,
6
1
1
1
57.92, 140.88, 133.28, 130.96, 128.48, 127.35,
25.98, 125.76 (2C), 125.67, 123.41, 119.21,
01.38, 97.93, 58.56, 30.95, 19.28.
1
The NMR for 5 follows: H (300 MHz,
DMSO-d , δ): 8.43 (d, J = 8.1 Hz, 1H), 7.95
6
(
7
dm, J = 7.7 Hz, 2H), 7.82 (d, J = 8.1 Hz, 1H),
.72 (tm, J = 7.0 Hz, 1H), 7.55 (m, 3H), 7.46
Results and discussion
(
d, J = 7.7 Hz, 1H), 7.41 (d, J = 7.7 Hz, 1H),
The X-ray investigations show that
molecules 4 and 5 have slightly different
structures, but most of the geometric parameters
7
1
1
1
1
1
.37 (br s, 2H), 7.32 (d, J = 7.0 Hz, 1H), 5.46 (s,
13
H); C (75 MHz, DMSO-d , δ): 159.56, 157.87,
6
57.82, 153.81, 152.11, 140.71, 133.30, 132.93,
30.96, 128.48, 127.45, 126.10, 125.85, 125.76,
24.74, 123.44, 122.46, 119.13, 116.61, 112.98,
04.68, 58.56, 31.46.
15
are very similar to the standard values and are
3–7
very close to our data.
In both molecules the pyran ring adopts
a flattened boat conformation: the O1 and C4
atoms are out of the C2/C3/C5/C9 plane (planar
˚
Crystallography
Single crystals of 4 and 5 were obtained
by slow evaporation of their ethanol and ace-
tonitrile solutions, respectively. Suitable colorless
crystals of 4 and 5 with approximate dimensions
within 0.003(3) and 0.020(4) A, respectively) by
˚
0
.041(3) and 0.043(3) A in 4 and −0.117(4) and
˚
−0.220(4) A in 5. The bending of the hetero-
cyclic rings along the lines O1· · ·C4, C2· · ·C9
◦
and C3· · ·C5 equals 4.0(3), 3.3(3) and 2.8(3)
◦
in 4, and 15.8(3), 9.4(3) and 14.3(3) in 5, re-
0
.60 × 0.19 × 0.13 and 0.48 × 0.10 × 0.08 mm
spectively. Thus, the heterocyclic ring is more
flattened in molecule 4. In both molecules, the
bulky naphthalene substituent occupies a pseudo-
axial position and the dihedral angle with the
flat part of the pyran ring is equal to 94.6(3)
were found. Diffraction data for 4 and 5 were
◦
collected at −173 C on a RIGAKU R-AXIS
RAPID diffractometer with graphite monochro-
˚
mator and CuK radiation (λ = 1.54118 A) us-
α
◦
ing a 0.8 mm collimator. Data collection, inten-
and 76.8(3) , respectively. The mutual orienta-
sity integration, and absorption corrections were
tion of these fragments and the flatness of the
heterocyclic rings (especially in 4) lead to H· · ·H
intramolecular steric interactions: H4A· · ·H18A
performed with the CrystalClear package.1
3
A
spherical-harmonics-based absorption correction
was applied by deducing an absorption surface
associated with the crystal, requiring that this
surface minimize the difference in intensities be-
tween symmetry related reflections.
All non-hydrogen atoms of the structures
were found by direct methods. Refinement was
done by full-matrix least-squares first isotropi-
cally and then anisotropically for all non-H atoms
˚
˚
1.98 A in 4 and 2.11 A in 5. These contacts are
shorter than the sum of the van der Waals radii of
16
the H atoms. As we mentioned earlier for related
6,7
compounds, such steric hindrance causes elon-
gation of the C4---C10 bond lengths to 1.556(3)
˚
and 1.542(4) A, respectively, in comparison with
3
2
neighboring Csp ---Csp distances that are only
slightly longer or equal to the standard value.
15

920
Nesterov, Wiedenfeld, Nesterova, and Daniels
Table 1. Structure Determination Summary for 4 and 5
4
5
CCDC deposit no.
Empirical formula
Formula weight
Diffractometer
Temperature, K
Crystal system
Space group; Z
256432
C20H14N2O3
330.33
256433
C23H14N2O3C2H3N
407.42
RIGAKU R-AXIS RAPID RIGAKU R-AXIS RAPID
100
100
Monoclinic
P21/n; 4
7.054(1)
8.822(1)
24.833(2)
90.00
94.30(4)
90.00
1541.0(3)
1.424
Monoclinic
P21/n; 4
11.075(1)
7.854(1)
22.703(2)
90
90.67(1)
90
1974.6(3)
1.370
˚
a (A)
˚
b (A)
˚
c (A)
◦
α ( )
◦
β ( )
◦
γ ( )
˚
3
Volume (A )
Density (g cm 3)
−
θ scan range
5.3–66.6
0.80
3.9–68.4
0.75
Absorbtion coefficient (mm 1)
−
Rmerge
0.059
0.063
Absorbtion correction factor
Total reflections
0.83–0.85
12402
0.69–0.94
12446
Independent reflections
Observed reflections [Fo > 4σ (Fo)]
Final R1
Final wR2
Goodness of fit
2570
2484
0.0605
0.1638
1.046
3495
3224
0.0750
0.2428
1.048
◦
In both molecules, the dihedral angle be-
5.3(3) and 7.1(3) , respectively. Due to the near
tween the flat part of the pyran ring and the fused
pyron heterocycle in 4 and the fused coumarin
heterocycle in 5 is small. This angle value is
planarity, it is possible to predict conjugation
throughout both rings. According to Table 2, the
Table 2. Selected Bond Distances in
Molecules 4 and 5
Bond
4
5
O(1) ---- C(2)
O(1) ---- C(9)
N(1) ---- C(2)
C(2) ---- C(3)
C(3) ---- C(1)
C(3) ---- C(4)
C(1) ---- N(2)
C(4) ---- C(5)
C(4) ---- C(10)
C(5) ---- C(6)
C(5) ---- C(9)
C(6) ---- O(3)
O(3) ---- C(7)
C(7) ---- C(8)
C(8) ---- C(9)
1.382(3) 1.384(3)
1.382(3) 1.368(3)
1.342(2) 1.339(4)
1.354(3) 1.346(4)
1.423(3) 1.428(4)
1.515(4) 1.516(4)
1.155(3) 1.153(4)
1.502(3) 1.511(4)
1.556(3) 1.542(4)
1.437(3) 1.445(4)
1.356(3) 1.343(4)
1.388(3) 1.370(3)
1.374(3) 1.378(3)
1.342(3) 1.396(4)
1.421(3) 1.447(4)
Fig. 3. Projection of the crystal packing of 4 along the a axis.
Dashed lines are intermolecular N--- H· · ·O and C--- H· · ·N H-
bonds.

C H N O and C H N O ·C H N
921
20
14
2
3
23 14
2
3
2
3
Table 3. Hydrogen-Bond Parameters for 4
d(D ---- H) d(H· · ·A) <DHA d(D· · ·A)
Table 4. Hydrogen-Bond Parameters for 5
d(D ---- H) D(H· · ·A) <DHA d(D· · ·A)
D--- H
A
D ---- H
A
N(1) ---- H(1B)
C(20) ---- H(20C)
0.88
0.98
2.05
2.55
145 2.820(3) O(2) [x, 1 + y, z]
155 3.463(3) N(2) [0.5 − x,
N(1) ---- H(1B)
C(22) ---- H(22A) 0.95
0.88
2.08
2.52
158
161
2.914(3) O(2) [x, y − 1, z]
3.435(4) N(2) [−0.5 + x,
0.5 − y, 0.5 + z]
−
0.5 + y, 0.5 − z]
C(2S) ---- H(1SC) 1.1(3)
2.41(3)
159(1) 3.448(4) N(1S) [0.5 − x,
0.5 + y, 0.5 − z]
bond length distributions show an alternation of
single C---C and double C -- -- -- C bond lengths and
also elongation of C -- -- -- O bonds in comparison with
normal values. Such bond lengths are consistent
with the idea of extensive conjugation in these
systems.
teractions can be considered to be weak H-bonds.
The acetonitrile molecules are linked via weak
C---H· · ·N intermolecular hydrogen bonds that
15
form infinite chains along the b axes (Fig. 4;
Table 4).
In both molecules, only one H-atom of the
NH group is involved in a N---H· · ·O inter-
2
molecular hydrogen bond. In the crystal of 4,
intermolecular hydrogen bonds N---H· · ·O and
C---H· · ·N link molecules into infinite tapes along
Acknowledgments
We thank the N.I.H (Grants S06 GM008066-
the b axis (Fig. 3; Table 3). In the crystals of
3
1 and 1 P20 MD001104-01 National Center on
5
, intermolecular hydrogen bonds N---H· · ·O and
Minority Health and Health Disparities) for gen-
erous financial support and the ACS-PRF for sup-
port for D.W. to attend the ACS-PRF summer
school on X-Ray Crystallography (UC San Diego,
August, 2004).
C---H· · ·N link molecules into infinite layers par-
allel to the bc plane (Fig. 4; Table 4). In both cases,
17
according to literature data, the C---H· · ·N in-
Supplementary material CCDC 256432 & 256433 contains the
supplementary crystallographic data for this paper. These data
can be obtained free of charge at www.ccdc.cam.ac.uk/conts/
retrieving.html of from the Cambridge Crystallographic Data Centre
(
CCDC), 12 Union Road, Cambridge CB2 1EZ, United Kingdom;
fax: +44(0)1223-336033; e-mail: deposit@ccdc.cam.ac.uk.
References
1
. Sharanina, L.G.; Nesterov, V.N.; Klokol, G.V.; Rodinovskaya,
L.A.; Shklover, V.E.; Sharanin, Yu.A.; Struchkov, Yu. T.;
Promonenkov, V.K. Zh. Org. Khim. 1986, 22, 1185.
2. Klokol, G.V.; Sharanina, L.G.; Nesterov, V.N.; Shklover, V.E.;
Sharanin, Yu.A.; Struchkov, Yu.T. Zh. Org. Khim. 1987, 23,
4
12.
3
4
5
6
7
8
. Nesterov, V.N.; Viltchinskaia, E.A. Acta Crystallogr. 2001,
C57, 616.
. Shestopalov, A.M.; Emelianova, Yu.M.; Nesterov, V.N. Russ.
Chem. Bull. 2002, 51, 2238.
. Shestopalov, A.M.; Emelianova, Yu.M.; Nesterov, V.N. Russ.
Chem. Bull. 2003, 52, 1164.
. Nesterov, V.N.; Wiedenfeld, D.J.; Nesterova, S.V.; Minton,
M.A. Acta Crystallogr. 2004, C60, o334.
. Nesterova, S.V.; Wiedenfeld, D.J.; Nesterov, V.N.. Acta Crys-
tallogr. 2004, C60, o559.
. Nesterov, V.N.; Kuleshova, L.N.; Antipin, M.Yu. Crystallogr.
Rep. 2001, 46, 402.
Fig. 4. Projection of the crystal packing of 5 along the a
axis (showed only one layer of molecules). Dashed lines are
intermolecular N--- H· · ·O and C--- H· · ·N H-bonds.

922
Nesterov, Wiedenfeld, Nesterova, and Daniels
9
. Nesterov, V.N.; Kuleshova, L.N.; Antipin, M.Yu. Crystallogr.
Rep. 2001, 46, 959.
14. Sheldrick, G.M. SHELXTL-97 V5.10 (Bruker AXS: Madison,
WI) 1997.
1
0. Li, A.H.; Ji, X.D.; Kim, H.S.; Melman, N.; Jacobson, K.A. Drug
Develop. Res. 1999, 48, 171.
15. Allen, F.H.; Kennard, O.; Watson, D.G.; Brammer, L.; Orpen,
A.G.; Taylor, R. J. Chem. Soc. Perkin Trans. 1987, 2,
S1.
1
1. Suarez, M.; Salfran, E.; Verdecia, Y.; Ochoa, E.; Alba, L.;
Martin, N.; Martinez, R.; Quinteiro, M.; Seoane, C.; Novoa,
H.; Blaton, N.; Peeters, O.M.; De Ranter, C. Tetrahedron 2002,
16. Rowland, R.S.; Taylor, R. J. Phys. Chem. 1996, 100,
7384.
5
8, 953.
17. Desiraju, G.R.; Steiner, T. The Weak Hydrogen Bond in Struc-
tural Chemistry and Biology; 1999, New York: Oxford Univer-
sity Press, Oxford.
1
1
2. Allen, F.N.; Kennard, O. Chem. Des. Auto. News. 1993, 8, 31.
3. CrystalClear user manual, Rigaku/MSC, Inc. (c) 2004.