Three sterically hindered 6-amino-5-cyano-2-methyl-4-(1-naphthyl)-4H-pyran- 3-carboxylate derivatives

Article abstract of DOI:10.1107/S0108270107049001

In the title compounds, 2-methoxy-ethyl 6-amino-5-cyano-2-methyl-4-(1- naphthyl)-4H-pyran-3-carboxyl-ate, C21H20N2O4, (II), isopropyl 6-amino-5-cyano-2-methyl-4-(1-naphthyl)-4H-pyran-3-carboxyl-ate, C21H20N2O3, (III), and ethyl 6-amino-5-cyano-2-methyl-4-(1-naphthyl)-4H-pyran-3-carboxyl- ate, C20H18N2O3, (IV), the heterocyclic pyran ring adopts a flattened boat conformation. In (II) and (III), the carbonyl group and a double bond of the heterocyclic ring are mutually anti, but in (IV) they are mutually syn. The ester O atoms in (II) and (III) and the carbonyl O atom in (IV) participate in intra-molecular C - H...O contacts to form six-membered rings. The dihedral angles between the naphthalene substituent and the closest four atoms of the heterocyclic ring are 73.3 (1), 71.0 (1) and 74.3 (1)° for (II)-(IV), respectively. In all three structures, only one H atom of the NH2 group takes part in N - H...O [in (II) and (III)] or N - H...N [in (IV)] inter-molecular hydrogen bonds, and chains [in (II) and (III)] or dimers [in (IV)] are formed. In (II), weak inter-molecular C - H...O and C - H...N hydrogen bonds, and in (III) inter-molecular C - H...O hydrogen bonds link the chains into ladders along the a axis. International Union of Crystallography 2007.

Full text of DOI:10.1107/S0108270107049001

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
very similar to standard values (Allen et al., 1987) and are very
close to our previous data for sterically hindered 4H-pyran
derivatives (Nesterov et al., 2004, 2005, and literature values
cited therein).
ISSN 0108-2701
Three sterically hindered 6-amino-
5-cyano-2-methyl-4-(1-naphthyl)-
4H-pyran-3-carboxylate derivatives
Vladimir N. Nesterov,* David J. Wiedenfeld, Svitlana V.
Nesterova and Lucas F. Hastings
Department of Natural Sciences, New Mexico Highlands University, Las Vegas,
NM 87701, USA
Correspondence e-mail: vnesterov@nmhu.edu
Received 29 August 2007
Accepted 5 October 2007
Online 14 November 2007
X-ray analysis shows that the title molecules have similar
structures, with the pyran ring adopting a ¯attened boat
conformation (Table 1). The dihedral angles between the
bulky pseudo-axial naphthalene substituent and the closest
four atoms (C2/C3/C5/C6) of the pyran ring are 73.3 (1),
71.0 (1) and 74.3 (1)ꢀ in (II), (III) and (IV), respectively. The
mutual orientation of these fragments and the ¯atness of the
heterocyclic rings lead to intramolecular HÁ Á ÁH steric inter-
In the title compounds, 2-methoxyethyl 6-amino-5-cyano-2-
methyl-4-(1-naphthyl)-4H-pyran-3-carboxylate, C21H20N2O4,
(II), isopropyl 6-amino-5-cyano-2-methyl-4-(1-naphthyl)-4H-
pyran-3-carboxylate, C21H20N2O3, (III), and ethyl 6-amino-
5-cyano-2-methyl-4-(1-naphthyl)-4H-pyran-3-carboxylate,
C20H18N2O3, (IV), the heterocyclic pyran ring adopts a
¯attened boat conformation. In (II) and (III), the carbonyl
group and a double bond of the heterocyclic ring are mutually
anti, but in (IV) they are mutually syn. The ester O atoms in
(II) and (III) and the carbonyl O atom in (IV) participate in
intramolecular CÐHÁ Á ÁO contacts to form six-membered
rings. The dihedral angles between the naphthalene substi-
tuent and the closest four atoms of the heterocyclic ring are
73.3 (1), 71.0 (1) and 74.3 (1)ꢀ for (II)±(IV), respectively. In all
three structures, only one H atom of the NH2 group takes part
in NÐHÁ Á ÁO [in (II) and (III)] or NÐHÁ Á ÁN [in (IV)]
intermolecular hydrogen bonds, and chains [in (II) and (III)]
or dimers [in (IV)] are formed. In (II), weak intermolecular
CÐHÁ Á ÁO and CÐHÁ Á ÁN hydrogen bonds, and in (III)
intermolecular CÐHÁ Á ÁO hydrogen bonds link the chains
into ladders along the a axis.
Ê
actions: H4AÁ Á ÁH15A = 2.08, 2.09 and 2.00 A in (II)±(IV),
respectively (Figs. 1±3). These contacts are shorter than the
Ê
sum of the van der Waals radii of H atoms (2.2 A; Rowland &
Taylor, 1996). As in related compounds (Nesterov et al., 2004,
2005), such steric hindrance causes elongation of the C4ÐC7
Ê
bond to 1.536 (2), 1.541 (2) and 1.531 (3) A, respectively, in
comparison with neighbouring Csp3ÐCsp2 distances. The
latter are only slightly longer than or are equal to the standard
Ê
value (1.507 A; Allen et al., 1987).
Comment
The present investigation is a continuation of our work on the
synthesis and structural study of sterically hindered hetero-
cyclic compounds, such as 4H-pyran derivatives (Nesterov et
al., 2004, 2005), that can be obtained starting from different
unsaturated nitriles (Nesterov et al., 2001a,b). Some 4H-pyran
derivatives are potential bioactive compounds, such as calcium
antagonists (Suarez et al., 2002) or potent apoptosis inducers
(Kemnitzer et al., 2004; Zhang et al., 2005).
Syntheses and X-ray structural investigations have been
carried out for compounds (II)±(IV) (Figs. 1±3), which were
synthesized by the reaction of (1-naphthylmethylene)-
malononitrile, (I), with different ꢀ-ketoesters. Most of the
geometric parameters in the molecules (Tables 2, 4 and 6) are
Figure 1
A view of compound (II), showing the atom numbering used.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii. Dashed lines
represent short intramolecular (C)HÁ Á ÁO and HÁ Á ÁH contacts, both of
Ê
2.08 A.
Acta Cryst. (2007). C63, o685±o689
DOI: 10.1107/S0108270107049001
# 2007 International Union of Crystallography o685

organic compounds
In (II) and (III), the C O group adopts an anti orientation
relative to the C2 C3 double bond [C2ÐC3ÐC18ÐO2 =
172.0 (2) and 157.7 (2)ꢀ, respectively]. However, in (IV) it has
a syn orientation [C2ÐC3ÐC18ÐO2 = 26.1 (3)ꢀ]. As seen in
Figs. 1±3, in (II) and (III) the O3 atoms of the ester groups and
in (IV) atom O2 of the carbonyl group have favourable
orientations for the formation of short steric intramolecular
contacts with the methyl groups of the heterocyclic ring (O3/
to literature data (Desiraju & Steiner, 1999), these contacts
can be considered weak hydrogen bonds. However, in these
cases it can be dif®cult to distinguish between a weak intra-
molecular hydrogen bond and a contact which is enforced by
the rigid molecular framework (Desiraju & Steiner, 1999). In
each case, the contact connects the atoms into a six-membered
ring. As in related compounds (Nesterov & Viltchinskaia,
2001; Nesterov et al., 2004), in all three title molecules there is
conjugation between the donor NH2 and acceptor CN groups
via the C5 C6 double bond. Thus, in all three molecules, the
C6ÐN1 bonds are shorter than the average conjugated CÐN
Ê
O2Á Á ÁH17A = 2.08, 2.24 and 2.27 A, respectively). According
Ê
single-bond length (1.370 A; Allen, 2002), but variations in the
other distances in these ¯at fragments are less distinct.
In all three compounds, only one H atom of the NH2 group
is involved in an NÐHÁ Á ÁO [(II) and (III)] or NÐHÁ Á ÁN
[(IV)] intermolecular hydrogen bond (Tables 3, 5 and 7) and
chains along the a axis are formed in (II) and (III) (Figs. 4 and
5). In (IV), the syn orientation of the C O group and its
participation in the intramolecular steric contacts with the H
Ê
atoms of the CH3 and CH2 groups (O2Á Á ÁH19A = 2.31 A), and
the different crystal packing, are reasons for the NÐHÁ Á ÁN
hydrogen bonds forming centrosymmetric dimers in the
crystal structure (Fig. 6). In addition, (II) exhibits weak C4Ð
H4AÁ Á Á O2 and C17ÐH17BÁ Á ÁN2 interactions and in (III),
C4ÐH4AÁ Á Á O2 intermolecular hydrogen bonds link the
chains along the a axis into ladders (Figs. 4 and 5; Tables 3
and 5).
Analysis of the crystal packing of the title compounds shows
Figure 2
that in (II) and (III) there are short intermolecular steric
Ê
z) = 3.302 (3) A and
A view of compound (III), showing the atom numbering used.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii. Dashed lines
represent short intramolecular (C)HÁ Á ÁO and HÁ Á ÁH contacts of 2.24 and
contacts [C2Á Á ÁC2(1
x, 1
x, y, 1
y, 1
Ê
C10Á Á ÁC10(2
z) = 3.377 (3) A in (II), and
Ê
2.09 A, respectively.
Figure 3
A view of compound (IV) showing the atom numbering used.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii. Dashed lines
represent short intramolecular (C)HÁ Á ÁO and HÁ Á ÁH contacts of 2.27 and
Figure 4
A projection of the crystal packing of (II) along the c axis. Dashed lines
represent intermolecular NÐHÁ Á ÁO and weak CÐHÁ Á ÁO and CÐHÁ Á ÁN
hydrogen bonds. H atoms not involved in these interactions have been
omitted for clarity.
Ê
2.00 A, respectively.
ꢁ
o686 Nesterov et al. C21H20N2O4, C21H20N2O3 and C20H18N2O3
Acta Cryst. (2007). C63, o685±o689

organic compounds
Ê
y, x) = 3.345 (3) A in (III)] between
atoms of the heterocycle or naphthalene fragments of neigh-
bouring molecules which are below the sum of the van der
C8Á Á ÁC9(1
x, 1
Experimental
The title compounds, (II)±(IV), were obtained by the reaction of
(1-naphthylmethylene)malononitrile, (I), with 2-methoxyethyl
acetoacetate, isopropyl acetoacetate and ethyl acetoacetate, respec-
tively, according to a literature procedure (Nesterov & Viltchinskaia,
2001; Nesterov et al., 2004). The resulting precipitates were isolated
and recrystallized from acetonitrile [m.p. 437 K and yield 75% for
(II); m.p. 451 K and yield 79% for (III); m.p. 417 K and yield 77% for
(IV)]. Crystals of the compounds were grown by slow isothermic
evaporation from absolute ethanol solutions. All compounds were
Ê
Waals radii of C (3.40 A; Rowland & Taylor, 1996). In (IV),
similar contacts are comparable with or slightly exceed the
sum of the van der Waals radii of C. Such steric intermolecular
contacts can play a role in determining the orientation of the
bulky naphthalene substituents in the molecules and can be
considered as ꢁ±ꢁ interactions between them in the crystal
structures (Figs. 4 and 5). The other geometric parameters in
compounds (II)±(IV) do not differ signi®cantly from standard
values (Allen et al., 1987).
1
characterized by H and 13C NMR spectroscopy.
Compound (II)
Crystal data
C21H20N2O4
Mr = 364.39
Triclinic, P1
a = 8.245 (2) A
b = 10.962 (3) A
ꢃ = 107.349 (7)ꢀ
3
Ê
V = 910.9 (4) A
Z = 2
Mo Kꢂ radiation
Ê
1
Ê
Ê
ꢄ = 0.09 mm
T = 100 (2) K
c = 11.008 (3) A
ꢂ = 98.391 (7)ꢀ
ꢀ = 100.819 (8)ꢀ
0.22 Â 0.17 Â 0.14 mm
Data collection
Bruker SMART APEXII CCD
area-detector diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.902, Tmax = 0.987
7926 measured re¯ections
3594 independent re¯ections
2533 re¯ections with I > 2ꢅ(I)
Rint = 0.029
Re®nement
R[F2 > 2ꢅ(F2)] = 0.043
wR(F2) = 0.111
S = 1.00
246 parameters
H-atom parameters constrained
3
Ê
Áꢆmax = 0.27 e A
3
Ê
0.26 e A
3594 re¯ections
Áꢆmin
=
Table 1
Geometric parameters (A, ꢀ) for the heterocyclic rings in compounds
(II)±(IV).
Ê
Á(C2/C3/C5/C6) is the r.m.s. deviation of the atoms from the least-squares
mean plane through the four atoms speci®ed.
Figure 5
A projection of the crystal packing of (III) along the b axis. Dashed lines
represent intermolecular NÐHÁ Á ÁO and weak CÐHÁ Á ÁO hydrogen
bonds. H atoms not involved in these interactions have been omitted for
clarity.
Plane/Compound
(II)
(III)
(IV)
Á(C2/C3/C5/C6)
Displacement of
atom O1 from
the plane
0.004 (1)
0.054 (1)
0.017 (1)
0.046 (1)
0.001 (1)
0.026 (1)
Displacement of
atom C4 from
the plane
0.115 (1)
0.066 (1)
0.028 (1)
Hinge angle
O1ÐC4
C2ÐC6
7.8 (1)
4.6 (1)
7.5 (1)
5.3 (1)
3.9 (1)
4.4 (1)
2.5 (1)
2.1 (1)
1.8 (1)
C3ÐC5
Table 2
Selected geometric parameters (A, ) for (II).
ꢀ
Ê
O2ÐC18
O3ÐC18
N1ÐC6
C2ÐC3
1.215 (2)
1.330 (2)
1.340 (2)
1.347 (2)
C3ÐC18
C4ÐC7
C5ÐC6
1.481 (2)
1.536 (2)
1.353 (2)
Figure 6
A projection of part of the crystal packing of (IV) along the b axis.
Dashed lines represent intermolecular NÐHÁ Á ÁN hydrogen bonds. H
atoms not involved in these interactions have been omitted for clarity.
C2ÐC3ÐC18ÐO2
171.95 (17)
C2ÐC3ÐC18ÐO3
7.9 (2)
ꢁ
Acta Cryst. (2007). C63, o685±o689
Nesterov et al.
C21H20N2O4, C21H20N2O3 and C20H18N2O3 o687

organic compounds
Table 3
Hydrogen-bond geometry (A, ) for (II).
Data collection
ꢀ
Ê
Bruker SMART APEXII CCD
area-detector diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.918, Tmax = 0.987
14847 measured re¯ections
3413 independent re¯ections
2184 re¯ections with I > 2ꢅ(I)
Rint = 0.078
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N1ÐH1BÁ Á ÁO2i
C4ÐH4AÁ Á ÁO2ii
C17ÐH17BÁ Á ÁN2iii
0.88
1.00
0.98
2.05
2.56
2.61
2.931 (2)
3.463 (3)
3.552 (2)
175
150
161
Re®nement
R[F2 > 2ꢅ(F2)] = 0.047
wR(F2) = 0.111
S = 1.00
228 parameters
H-atom parameters constrained
Symmetry codes: (i)
z ‡ 1.
x
1; y; z; (ii) x ‡ 2; y ‡ 1; z ‡ 1; (iii) x ‡ 1, y ‡ 1,
3
Ê
Áꢆmax = 0.27 e A
3
Ê
0.22 e A
3413 re¯ections
Áꢆmin
=
Compound (III)
Table 6
Selected geometric parameters (A, ) for (IV).
ꢀ
Ê
Crystal data
O2ÐC18
O3ÐC18
N1ÐC6
C2ÐC3
1.209 (2)
1.334 (2)
1.346 (2)
1.336 (3)
C3ÐC18
C4ÐC7
C5ÐC6
1.490 (3)
1.531 (3)
1.351 (3)
C21H20N2O3
Mr = 348.39
Triclinic, P1
ꢃ = 79.069 (7)ꢀ
3
Ê
V = 901.9 (6) A
Z = 2
Mo Kꢂ radiation
Ê
a = 8.248 (3) A
1
Ê
b = 11.184 (4) A
ꢄ = 0.09 mm
T = 100 (2) K
C2ÐC3ÐC18ÐO2
26.1 (3)
C2ÐC3ÐC18ÐO3
155.87 (18)
Ê
c = 11.394 (4) A
ꢂ = 63.646 (7)ꢀ
ꢀ = 73.836 (8)ꢀ
0.20 Â 0.16 Â 0.01 mm
Table 7
Hydrogen-bond geometry (A, ) for (IV).
Data collection
ꢀ
Ê
Bruker SMART APEXII CCD
area-detector diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.913, Tmax = 0.999
7635 measured re¯ections
3528 independent re¯ections
2682 re¯ections with I > 2ꢅ(I)
Rint = 0.030
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N1ÐH1AÁ Á ÁN2i
0.88
2.14
2.999 (2)
165
Symmetry code: (i) x; y ‡ 1; z ‡ 1.
Re®nement
R[F2 > 2ꢅ(F2)] = 0.053
wR(F2) = 0.148
S = 1.01
238 parameters
H-atom parameters constrained
For all three title compounds, H atoms were placed in geome-
trically calculated positions and re®ned using a riding model, with
3
Ê
Áꢆmax = 0.38 e A
3
Ê
0.23 e A
3528 re¯ections
Áꢆmin
=
Ê
CÐH = 0.95 A and Uiso(H) = 1.2Ueq(C) for aromatic, CÐH = 0.98 A
Ê
and Uiso(H) = 1.5Ueq(C) for CH3 (AFIX 137 in SHELXTL; Shel-
Ê
drick, 2001), CÐH = 0.99 A and Uiso(H) = 1.2Ueq(C) for CH2, and
Ê
CÐH = 1.00 A and Uiso(H) = 1.2Ueq(C) for CH groups, and NÐH =
Table 4
Selected geometric parameters (A, ) for (III).
ꢀ
Ê
Ê
0.88 A and Uiso(H) = 1.2Ueq(N) for the NH2 group.
O2ÐC18
O3ÐC18
N1ÐC6
C2ÐC3
1.219 (2)
1.338 (2)
1.343 (2)
1.345 (3)
C3ÐC18
C4ÐC7
C5ÐC6
1.482 (3)
1.541 (2)
1.359 (3)
For all compounds, data collection: APEX2 (Bruker, 2005); cell
re®nement: SAINT-Plus (Bruker, 2001); data reduction: SAINT-
Plus; program(s) used to solve structure: SHELXTL (Sheldrick,
2001); program(s) used to re®ne structure: SHELXTL; molecular
graphics: SHELXTL; software used to prepare material for publi-
cation: SHELXTL.
C2ÐC3ÐC18ÐO2
157.71 (17)
C2ÐC3ÐC18ÐO3
23.8 (2)
The authors thank the NIH (grant No. 1 P20 MD001104-01)
for generous ®nancial support, and the NSF/DMR for support
(grant No. 0420863) for the acquisition of a single-crystal
X-ray diffractometer.
Table 5
Hydrogen-bond geometry (A, ) for (III).
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N1ÐH1BÁ Á ÁO2i
0.88
1.00
2.12
2.40
2.989 (2)
3.325 (3)
168
154
C4ÐH4AÁ Á ÁO2ii
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: BM3039). Services for accessing these data are
described at the back of the journal.
Symmetry codes: (i) x 1; y; z; (ii) x ‡ 1; y ‡ 1; z ‡ 1.
References
Compound (IV)
Allen, F. H. (2002). Acta Cryst. B58, 380±388.
Crystal data
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor,
R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1±19.
Bruker (2001). SAINT-Plus for Windows NT. Version 6.2. Bruker AXS Inc.,
Madison, Wisconsin, USA.
Bruker (2005). APEX2. Version 1.27. Bruker AXS Inc., Madison, Wisconsin,
USA.
3
Ê
C20H18N2O3
Mr = 334.36
Monoclinic, P21=c
Ê
a = 7.8638 (7) A
b = 19.4628 (18) A
Ê
c = 11.0823 (10) A
ꢀ = 99.963 (2)ꢀ
V = 1670.6 (3) A
Z = 4
Mo Kꢂ radiation
1
ꢄ = 0.09 mm
T = 100 (2) K
Ê
Desiraju, G. R. & Steiner, T. (1999). The Weak Hydrogen Bond. Oxford
University Press.
0.20 Â 0.16 Â 0.14 mm
ꢁ
o688 Nesterov et al. C21H20N2O4, C21H20N2O3 and C20H18N2O3
Acta Cryst. (2007). C63, o685±o689

organic compounds
Kemnitzer, W., Drewe, J., Jiang, S., Zhang, H., Wang, Y., Zhao, J., Jia, S.,
Herich, J., Labreque, D., Storer, R., Meerovitch, K., Bouffard, D., Rej, R.,
Denis, R., Blais, C., Lamothe, S., Attardo, G., Gourdeau, H., Tseng, B.,
Kasibhatla, S. & Cai, S. X. (2004). J. Med. Chem. 47, 6299±6310.
Nesterov, V. N., Kuleshova, L. N. & Antipin, M. Yu. (2001a). Crystallogr. Rep.
46, 402±410.
Nesterov, V. N. & Viltchinskaia, E. A. (2001). Acta Cryst. C57, 616±618.
Rowland, R. S. & Taylor, R. (1996). J. Phys. Chem. 100, 7384±7391.
Sheldrick, G. M. (2001). SHELXTL. Version 6.12 for Windows NT. Bruker
AXS Inc., Madison, Wisconsin, USA.
Sheldrick, G. M. (2003). SADABS. Version 2.03. Bruker AXS Inc., Madison,
Wisconsin, USA.
Nesterov, V. N., Kuleshova, L. N. & Antipin, M. Yu. (2001b). Crystallogr. Rep.
46, 959±965.
Nesterov, V. N., Wiedenfeld, D. J., Nesterova, S. V. & Daniels, L. M. (2005).
J. Chem. Crystallogr. 35, 917±922.
Nesterov, V. N., Wiedenfeld, D. J., Nesterova, S. V. & Minton, M. A. (2004).
Acta Cryst. C60, o334±o337.
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. (2002). Tetrahedron, 58, 953±960.
Zhang, H.-Z., Kasibhatla, S., Kuemmerle, J., Kemnitzer, W., Ollis-Mason, K.,
Qiu, L., Crogan-Grundy, C., Tseng, B., Drewe, J. & Cai, S. X. (2005). J. Med.
Chem. 48, 5215±5223.
ꢁ
Acta Cryst. (2007). C63, o685±o689
Nesterov et al.
C21H20N2O4, C21H20N2O3 and C20H18N2O3 o689