Ethyl 6-amino-2-methoxypyridine-3-carboxylate, interplay of molecular and supramolecular structure

Article abstract of DOI:10.1107/S0108270101010228

The title compound, C₉H₁₂N₂O₃, crystallizes with two molecules in the asymmetric unit. There is extensive hydrogen bonding which results in the formation of a two-dimensional corrugated sheet. This supramolecular structure is determined by the formation of hydrogen-bonded chains resulting from the presence of a 6-amino group and an ethoxycarbonyl group as substituents on a pyridine ring in relative para positions which constitute a π-electron 'push-pull' system.

Full text of DOI:10.1107/S0108270101010228

organic compounds
Acta Crystallographica Section C
Crystal Structure
(Table 2) and is hence the stronger. The two molecules have
similar bond lengths and angles.
Communications
ISSN 0108-2701
Ethyl 6-amino-2-methoxypyridine-
3-carboxylate, interplay of molecular
and supramolecular structure
The pyridine rings, while are essentially planar, show
deviations from regular hexagonal geometry (Table 1). In both
molecules, the CÐNH2 groups lie in the plane of the pyridine
ring. The N atoms have predominantly sp2-character, as is
Celeste Garcia,a Antonio Quesada,a Manuel Melguizo,a
a
a
a
Â
Justo Cobo, Manuel Nogueras, Adolfo Sanchez, Debbie
Ê
Cannonb and John Nicolson Lowc*
shown by the CÐN bond lengths [N12ÐC12 1.3449 (16) A
Ê
and N22ÐC22 1.3406 (17) A], which are shorter than the
Ê
mean value (1.360 A) reported for planar amino groups
bonded to aromatic systems (Allen et al., 1987). It is also
Ê
noteworthy that the C151ÐO15 [1.2115 (15) A] and C251Ð
Ê
O25 bonds [1.2162 (15) A] are long compared with the mean
Ê
(1.202 A; Schweizer & Dunitz, 1982) for other carbonyl
groups in aromatic carboxylic esters.
The compensation by the 6-amino lone pair for the
ꢀ-electron de®ciency of the 3-carboxylate group produces an
increase in the acidity of the amino H atoms, as well as an
enhancement of the electron density of the carbonyl O atom.
The partial charges thus developed favour the formation of
NÐHÁ Á ÁO C hydrogen bonds, which was con®rmed by an
analysis of the hydrogen bonding. This indicates the great
contribution of canonical form (Ia) (see scheme opposite) and
hence this can be considered as an example of resonance-
assisted hydrogen bonding (Gilli et al., 1989).
a
Â
Â
Â
Â
Departamento de Quõmica Inorganica y Organica, Universidad de Jaen, 23071
Jaen, Spain, bElectronic Engineering and Physics, University of Dundee, Dundee
DD1 4HN, Scotland, and cDepartment of Chemistry, University of Aberdeen, Meston
Walk, Old Aberdeen AB24 3UE, Scotland.
Â
Correspondence e-mail: jnlow111@hotmail.com
Received 29 May 2001
Accepted 20 June 2001
The title compound, C9H12N2O3, crystallizes with two mol-
ecules in the asymmetric unit. There is extensive hydrogen
bonding which results in the formation of a two-dimensional
corrugated sheet. This supramolecular structure is determined
by the formation of hydrogen-bonded chains resulting from
the presence of a 6-amino group and an ethoxycarbonyl group
as substituents on a pyridine ring in relative para positions
which constitute a ꢀ-electron `push±pull' system.
The supramolecular structure of (I) consists of corrugated
two-dimensional sheets formed by linked hydrogen-bonded
antiparallel chains formed by hydrogen bonding the dimers,
described above, together in a head-to-tail fashion. These
sheets lie in the (010) plane. Individual sheets are not linked to
neighbouring sheets. The dimers are connected by an N22Ð
Comment
The title compound, (I), was obtained through a hetero-Diels±
Alder/retro-Diels±Alder transformation of 4-amino-2-
methoxy-3-methylpyrimidin-4(3H)-one (acting as 2-azadiene)
and ethyl propiolate (acting as dienophile) (see reaction
scheme below), and the presence of a 6-amino group and an
ethoxycarbonyl group as substituents on a pyridine ring in
relative para positions constitutes a clear ꢀ-electron `push±
pull' system which explains the main structural features found
in the crystal structure.
The two unique molecules in the asymmetric unit were
chosen to give a dimer formed by the three-centred R21(6)
(Bernstein et al., 1995) hydrogen bond between the amino H
atom attached to N21 in molecule 1, and O25 and O26 in
molecule 2 (Fig. 1); the sum of the angles at the H atom is 353ꢀ.
The former of these two hydrogen bonds is the shorter
Figure 1
A view of (I) with the atomic numbering scheme. Displacement ellipsoids
are drawn at the 30% probability level. The dimer selected as the
asymmetric unit is shown with the three-centred hydrogen bond between
N12ÐH12BÁ Á ÁO26 and N12ÐH12BÁ Á ÁO25 forming an R12(6) ring motif.
ꢁ
Acta Cryst. (2001). C57, 1103±1105
# 2001 International Union of Crystallography
Printed in Great Britain ± all rights reserved 1103

organic compounds
H22BÁ Á ÁO15( 1 + x, y, 1 + z) hydrogen bond, producing via
the N12ÐH12BÁ Á ÁO25 bond, a C22(16) chain which runs
parallel to [101]. The C22(14) chain via O26 is shorter but, as
mentioned above, the N12ÐH12BÁ Á ÁO25 bond is the stronger
of the pair. Crystallographic symmetry produces an alter-
nating pattern of antiparallel chains which are linked to
neighbouring chains in two distinct ways. The ®rst linkage is
SAVZEU, in which the asymmetric unit, like that of (I),
contains two molecules, the chain is of the C22(16) type, as in
(I), and antiparallel chains are linked to form a ribbon
consisting of alternating R44(36) and R42(8) rings. Thus,
produced by an N22ÐH22AÁ Á ÁN11( 1 x,
y,
z)
hydrogen bond, which produces a ribbon with alternating
centrosymmetric R44(20) and R44(16) rings (Bernstein et al.,
1995) centred on the inversion centres at ( 12,0,0) and (0,0,21),
respectively (Fig. 2). The second linkage is produced by an
N12ÐH12AÁ Á ÁO25( x, y, z) hydrogen bond, the ribbon
so produced being made up of alternating centrosymmetric
R24(8) and R44(32) rings (Bernstein et al., 1995) centred on the
centres of inversion at (0,0,0) and (12,0,21), respectively (Fig. 3).
The following related compounds were retrieved from the
Cambridge Structural Database (CSD; Allen & Kennard,
1993): SAVZEU, ethyl 2-N-(6-amino-5-cyano-3-ethoxycar-
bonylpyridin-2-yl)aminobenzoate, C18H18N4O4 (Deady et al.,
1989); ZIVHAN, 2-amino-6-methoxy-4,5-bis(methoxycar-
bonyl)pyridine, C10H12N2O5 (Low et al., 1996); ZIVHER,
2-amino-4,5-bis(methoxycarbonyl)-6-(methylthio)pyridine,
C10H12N2O4S (Low et al., 1996). These are the only pyridine
compounds with a 2-amino group para to a 5-carboxylate
group (6-amino and 3-carboxylate in the numbering of the
title compound) and they all crystallize in space group P1, like
compound (I). These are all push±pull systems similar to (I)
and, in all cases, formation of NÐHÁ Á ÁO C hydrogen bonds
is observed. These hydrogen bonds form C(8) chains in
ZIVHAN and ZIVHER, which have only one molecule in the
asymmetric unit. Antiparallel chains link together to form a
ribbon consisting of alternating R22(14) and R42(18) rings. In
Figure 3
The molecular ribbon produced by the linking of antiparallel C22(14)
chains via the N12ÐH22AÁ Á ÁO25* hydrogen bond, showing the
alternating centrosymmetric R42(8) and R44(32) rings. Atoms labelled with
primes (0), asterisks (*) and hashes (#) are at (1 + x, y, 1 + z), ( x, y,
z) and (1 x, y, 1 z), respectively.
although ribbons are formed in all these structures, only in (I)
do they combine to form a sheet structure.
Experimental
Ethyl propiolate (0.95 g, 9.5 mmol) was added to a suspension of
6-amino-2-methoxypyrimidin-4(3H)-one (0.50 g, 3.2 mmol) in dry
dioxane (3 ml) and the reaction mixture was stirred at 393 K for 62 h.
The resulting dark solution was evaporated in vacuo to dryness and
the title compound was isolated and puri®ed by ¯ash-column chro-
matography on silica gel using dichloromethane/acetone mixtures in
an acetone gradient as eluent. Recrystallization from acetone
produced colourless crystals (yield: 48%, m.p. 396±397 K). Analysis
calculated for C9H12N2O3: C 55.1, H 6.2, N 14.3%; found: C 54.8,
H 6.0, N 14.1%.
Crystal data
C9H12N2O3
Mr = 196.21
Triclinic, P1
a = 7.4906 (2) A
b = 10.2409 (2) A
Z = 4
Dx = 1.367 Mg m
Mo Kꢁ radiation
3
Ê
Cell parameters from 4295
re¯ections
Ê
Ê
c = 13.1449 (3) A
ꢄ = 3.0±27.5ꢀ
ꢅ = 0.10 mm
T = 150 (1) K
1
ꢁ = 104.9607 (9)ꢀ
ꢂ = 90.7398 (9)ꢀ
ꢃ = 101.2452 (9)ꢀ
Block, colourless
0.40 Â 0.25 Â 0.15 mm
3
Ê
V = 953.34 (4) A
Data collection
Nonius KappaCCD diffractometer
' scans, and ! scans with ꢆ offsets
Absorption correction: multi-scan
(DENZO±SMN; Otwinowski &
Minor, 1997)
Tmin = 0.960, Tmax = 0.985
14 744 measured re¯ections
4295 independent re¯ections
3541 re¯ections with I > 2ꢇ(I)
Rint = 0.061
ꢄmax = 27.5ꢀ
Figure 2
The molecular ribbon produced by the linking of antiparallel C22(14)
chains via the N22ÐH22AÁ Á ÁN11* hydrogen bond, showing the
alternating centrosymmetric R44(20) and R44(16) rings. Atoms labelled
with primes (0), asterisks (*) and hashes (#) are at (1 + x, y, 1 + z),
h = 9 ! 9
k = 13 ! 12
l = 16 ! 17
Intensity decay: negligible
(
1
x, y, z) and ( x, y, 1 z), respectively.
ꢁ
1104 Celeste Garcia et al.
C9H12N2O3
Acta Cryst. (2001). C57, 1103±1105

organic compounds
Re®nement
H atoms were treated as riding atoms with CÐH distances in the
Ê
Ê
Re®nement on F2
R[F2 > 2ꢇ(F2)] = 0.051
wR(F2) = 0.142
S = 1.05
4295 re¯ections
w = 1/[ꢇ2(Fo2) + (0.0940P)2
+ 0.1054P]
range 0.95±0.99 A and NÐH distances of 0.88 A. The positions of the
methyl and amino H atoms were con®rmed by a difference map.
Data collection: KappaCCD Server Software (Nonius, 1997); cell
re®nement: DENZO±SMN (Otwinowski & Minor, 1997); data
reduction: DENZO±SMN; program(s) used to solve structure:
SHELXS97 (Sheldrick, 1997); program(s) used to re®ne structure:
SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII
(Johnson, 1976) and PLATON (Spek, 2000); software used to
prepare material for publication: SHELXL97 and WordPerfect
macro PRPKAPPA (Ferguson, 1999).
where P = (Fo2 + 2Fc2)/3
(Á/ꢇ)max < 0.001
3
Ê
Áꢈmax = 0.37 e A
Áꢈmin
3
Ê
0.42 e A
258 parameters
H-atom parameters constrained
=
Extinction correction: SHELXL97
Extinction coef®cient: 0.155 (12)
Table 1
Selected geometric parameters (A, ).
ꢀ
X-ray data were collected at the EPSRC, X-ray Crystal-
lographic Service, University of Southampton, using an Enraf±
Nonius KappaCCD diffractometer. The authors thank the
staff for all their help and advice.
Ê
N11ÐC16
N11ÐC12
C12ÐN12
C12ÐC13
C13ÐC14
C14ÐC15
C15ÐC16
C15ÐC151
C151ÐO15
1.3311 (16)
1.3525 (15)
1.3449 (16)
1.4086 (18)
1.3681 (18)
1.4084 (17)
1.4034 (18)
1.4725 (17)
1.2115 (15)
N21ÐC26
N21ÐC22
C22ÐN22
C22ÐC23
C23ÐC24
C24ÐC25
C25ÐC26
C25ÐC251
C251ÐO25
1.3268 (17)
1.3500 (16)
1.3406 (17)
1.4159 (19)
1.3607 (18)
1.4045 (17)
1.4113 (18)
1.4660 (18)
1.2162 (15)
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GD1162). Services for accessing these data are
described at the back of the journal.
References
C16ÐN11ÐC12
N12ÐC12ÐC13
C14ÐC13ÐC12
C13ÐC14ÐC15
C16ÐC15ÐC14
N11ÐC16ÐC15
118.41 (11)
121.18 (11)
118.24 (11)
121.18 (12)
115.92 (11)
124.21 (11)
C26ÐN21ÐC22
N21ÐC22ÐC23
C24ÐC23ÐC22
C23ÐC24ÐC25
C24ÐC25ÐC26
N21ÐC26ÐC25
118.90 (11)
121.81 (12)
117.74 (11)
122.07 (12)
115.54 (12)
123.89 (11)
Allen, F. H. & Kennard, O. (1993). Chem. Des. Autom. News, 8, 1, 31±37.
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor,
R. J. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1±19.
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem.
Int. Ed. Engl. 34, 1555±1573.
Deady, L. W., Mackay, M. F. & Werden, D. M. (1989). J. Heterocycl. Chem. 26,
161±168.
Ferguson, G. (1999). PRPKAPPA. University of Guelph, Canada.
Gilli, G., Belluci, F., Ferreti, V. & Bertolasi, V. (1989). J. Am. Chem. Soc. 111,
1023±1028.
Johnson, C. K. (1976). ORTEPII. Report ORNL-5138. Oak Ridge National
Laboratory, Tennessee, USA.
Low, J. N., Ferguson, G., Cobo, J., Melguizo, M., Nogueras, M. & Sanchez, A.
(1996). Acta Cryst, C52, 143±145.
Nonius (1997). KappaCCD Server Software. Windows 3.11 Version. Nonius
BV, Delft, The Netherlands.
Table 2
Hydrogen-bonding geometry (A, ).
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N12ÐH12AÁ Á ÁO25i
N12ÐH12BÁ Á ÁO26
N12ÐH12BÁ Á ÁO25
N22ÐH22AÁ Á ÁN11ii
N22ÐH22BÁ Á ÁO15iii
0.88
0.88
0.88
0.88
0.88
2.23
2.41
2.30
2.37
2.14
3.0543 (15)
3.1574 (14)
3.0250 (14)
3.2167 (17)
2.9791 (16)
156
143
139
162
160
Otwinowski, Z. & Minor, W. (1997). Methods Enzymol. 276, 307±326.
Schweizer, W. B. & Dunitz, J. D. (1982). Helv. Chim. Acta, 65, 1547±1554.
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Gott-
È
ingen, Germany.
Spek, A. L. (2000). PLATON. Version of May 2000. University of Utrecht,
The Netherlands.
Symmetry codes: (i) x; y; z; (ii)
1
x; y; z; (iii) x 1; y; z 1.
ꢁ
Acta Cryst. (2001). C57, 1103±1105
Celeste Garcia et al. C9H12N2O3 1105