2-Amino-4-chloro-5-formyl-6-[methyl(2-methylphenyl)amino]pyrimidine and 2-amino-4-chloro-5-formyl-6[(2-methoxyphenyl)methylamino]pyrimidine are isostructural and form hydrogen-bonded sheets of R22(8) and R66(32)

Article abstract of DOI:10.1107/S0108270108040481

An experiment was conducted to demonstrate that 2-Amino-4-chloro-5-formyl-6-[methyl-(2-methylphenyl)amino]pyrimidine and 2-amino-4-chloro-5-formyl-6-[(2-methoxyphenyl)methylamino]-pyrimidine are isostructural and form hydrogen-bonded sheets of R²

Full text of DOI:10.1107/S0108270108040481

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
conformations are denoted A and B, respectively. For both
conformers, examples were observed in which the pyrimidine
rings were planar within experimental uncertainty, while in
others these rings were significantly puckered into boat, screw-
boat or twist-boat conformations. The puckering of the pyri-
dine rings in these examples did not appear to inhibit to any
degree the development of the polarized electronic structures,
exactly as found in other heavily substituted pyrimidines
previously reported (Low et al., 2007; Melguizo et al., 2003;
Quesada et al., 2003, 2004; Trilleras et al., 2007). In all, of the 12
compounds previously studied, nine had formyl conformations
of type A and three of type B; independently, five of them
contained planar pyrimidine rings and seven contained
puckered rings.
ISSN 0108-2701
2-Amino-4-chloro-5-formyl-6-[methyl-
(2-methylphenyl)amino]pyrimidine
and 2-amino-4-chloro-5-formyl-6-
[(2-methoxyphenyl)methylamino]-
pyrimidine are isostructural and form
hydrogen-bonded sheets of R22(8) and
R66(32) rings
Jorge Trilleras,a Jairo Quiroga,a Justo Cobob and
Christopher Glidewellc*
a
´
´
´
Grupo de Investigacion de Compuestos Heterocıclicos, Departamento de Quımica,
b
´
Universidad de Valle, AA 25360 Cali, Colombia, Departamento de Quımica
Inorganica y Organica, Universidad de Jaen, 23071 Jaen, Spain, and cSchool of
Chemistry, University of St Andrews, Fife KY16 9ST, Scotland
Correspondence e-mail: cg@st-andrews.ac.uk
´
´
´
´
Received 1 December 2008
Accepted 1 December 2008
Online 13 December 2008
2-Amino-4-chloro-5-formyl-6-[methyl(2-methylphenyl)amino]-
pyrimidine, C13H13ClN4O, (I), and 2-amino-4-chloro-5-formyl-
6-[(2-methoxyphenyl)methylamino]pyrimidine,C13H13ClN4O2,
(II), are isostructural and essentially isomorphous. Although
the pyrimidine rings in each compound are planar, the ring-
substituent atoms show significant displacements from this
plane, and the bond distances provide evidence for polariza-
tion of the electronic structures. In each compound, a
combination of N—Hꢀ ꢀ ꢀN and N—Hꢀ ꢀ ꢀO hydrogen bonds
links the molecules into sheets built from centrosymmetric
R22(8) and R66(32) rings. The significance of this study lies in its
observation of the isostructural nature of (I) and (II), and in
the comparison of their crystal and molecular structures with
those of analogous compounds.
As a continuation of this study, we have now investigated
two further examples, (I) and (II), which both turn out to have
type B conformations and to contain planar pyrimidine rings.
Compounds (I) and (II) were prepared by selective mono-
substitution (Taylor & Gillespie, 1992; Quiroga et al., 2008) of
the 6-chloro substituent in 2-amino-4,6-dichloro-5-formyl-
pyrimidine (Seela & Sterker, 1986), and their constitutions
differ only in the identity of the substituent in the aryl ring, i.e.
2-methyl in (I) and 2-methoxy in (II) (Figs. 1 and 2).
Compounds (I) and (II) crystallize in the same space group
with fairly similar unit-cell dimensions; the coordinates of
corresponding atoms are also similar, while the patterns of the
hydrogen bonds are identical (Table 2). Accordingly, the
compounds are isostructural and effectively isomorphous.
The corresponding bond distances and torsion angles for (I)
and (II) are very similar (Table 1). The distances show many of
the characteristics observed previously in other compounds of
this type (Cobo et al., 2008). Thus, the ring distances N1—C2
and C6—N1 and the exocyclic distances C2—N2 are all very
similar, while the ring distances N3—C4 are, by some margin,
Comment
We have recently reported the molecular and supramolecular
structures of a number of N6-substituted 2-amino-4-chloro-5-
formylpyrimidines (Cobo et al., 2008). Two features of the
molecular structures that vary independently amongst the 12
examples studied are the orientation of the formyl group and
the shape of the pyrimidine ring, while in all cases the bond
distances provide strong evidence for the development of
polarized electronic structures. In the majority of the
compounds studied earlier (Cobo et al., 2008), the formyl
orientation has the formyl C—H bond approximately parallel
to the C—Cl bond, while in the remainder, the formyl C
bond is approximately parallel to the C—Cl bond; these two
O
Acta Cryst. (2009). C65, o11–o14
doi:10.1107/S0108270108040481
# 2009 International Union of Crystallography o11

organic compounds
the shortest of all the N—C distances; the formyl C51—O51
bonds are long for their type [mean value (Allen et al., 1987)
C51 and N61 are displaced to alternate sides of the ring plane,
with the central substituent atom C51 showing much the
largest displacement in each compound (Table 1). Methoxy
atom C68 in (II) is almost coplanar with the adjacent benzene
ring, having a deviation from the ring plane of only
˚
1.192 A], while the C5—C51 bonds are short (mean value =
˚
1.488 A). Taken together these distances provide evidence for
an important contribution to the overall electronic structures
in (I) and (II) from the polarized forms (Ia) and (IIa). This is
so despite the fact that the formyl O atom is not coplanar with
the pyrimidine ring, as indicated by the non-zero values of the
C4—C5—C51—O51 torsion angle (Table 1).
Although the pyrimidine ring in each of (I) and (II) is
essentially planar, with the maximum deviation of a ring atom
from the mean plane occurring in each compound for atom
˚
0.013 (4) A; accordingly, the two exocyclic C—C—O angles
associated with the methoxy substituent differ by ca 10ꢁ, as
normally observed in such cases.
Compounds (I) and (II) exhibit identical patterns of
hydrogen bonding (Table 2), with similar dimensions for the
hydrogen bonds in the two compounds. The N—Hꢀ ꢀ ꢀN
hydrogen bond generates a centrosymmetric R22(8) (Bernstein
1
2
˚
C5, displaced from the plane by 0.042 (3) A in (I) and
et al., 1995) motif, centred at (0, 0, ). The action of the N—
Hꢀ ꢀ ꢀO hydrogen bond is to link this dimeric unit at (0, 0, 12 ) to
˚
0.048 (3) A in (II), the substituent atoms attached to the
pyrimidine ring all show significant deviations from the ring
plane. In particular, the three adjacent substituent atoms Cl4,
1
1
1
1
the four adjacent dimers centred at (ꢂ , ꢂ , 0), (ꢂ , , 0),
2
2
2
2
(12, ꢂ , 1) and (12, , 1), thereby generating a sheet parallel to
1 1
2
2
(101) and built from alternating R22(8) and R66(32) rings (Fig. 3),
in which both ring types are centrosymmetric. There are no
direction-specific interactions between adjacent sheets; in
particular, both C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bonds and
aromatic ꢀ–ꢀ stacking interactions are absent, nor does the
methoxy O atom in (II) play any part in the hydrogen bonding.
Within the hydrogen-bonded sheets formed in each of (I)
and (II) there is a fairly short N—Hꢀ ꢀ ꢀCl contact (Table 2).
¨
However, it has been amply shown (Aakeroy et al., 1999;
Brammer et al., 2001; Thallapally & Nangia, 2001) that Cl
atoms covalently bonded to C atoms are very poor hydrogen-
bond acceptors and that such contacts are probably no more
than ordinary van der Waals contacts. It is thus safer to regard
the N—Hꢀ ꢀ ꢀCl contacts in (I) and (II) as adventitious contacts
consequent upon the geometry of the N—Hꢀ ꢀ ꢀO hydrogen
bonds and not of themselves structurally significant. In any
event, such an interaction would not have any bearing on the
overall forms of the hydrogen-bonded structures.
Of the analogues studied previously (Cobo et al., 2008),
those closest in constitution to (I) and (II) are (III), which
differs from (I) and (II) only in carrying no substituent on the
phenyl ring, and (IV), which is an isomer of (I). Compounds
(III) and (IV) both adopt type B conformations, but while
(III) contains a planar pyrimidine ring, in (IV) this ring adopts
a boat conformation. Although dimers characterized by R22(8)
Figure 1
The molecular structure of (I), showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 30% probability level.
Figure 3
Figure 2
The molecular structure of (II), showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 30% probability level.
Stereoview of the crystal structure of (I), showing the formation of a
hydrogen-bonded sheet of R22(8) and R66(32) rings parallel to (101). For
the sake of clarity, H atoms bonded to C atoms have been omitted.
ꢃ
o12 Trilleras et al.
C13H13ClN4O and C13H13ClN4O2
Acta Cryst. (2009). C65, o11–o14

organic compounds
motifs and built from paired N—Hꢀ ꢀ ꢀN hydrogen bonds can
be identified in the structures of each of (III) and (IV), just as
in (I) and (II), the further linking of these dimeric units in (III)
and (IV) does not resemble that in (I) and (II). In (III), a
combination of N—Hꢀ ꢀ ꢀN and C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen
bonds leads to the formation of a chain of edge-fused rings,
but the formyl O atom plays no role in the hydrogen bonding.
In (IV), by contrast, a combination of N—Hꢀ ꢀ ꢀN and N—
Hꢀ ꢀ ꢀO hydrogen bonds generates a chain of alternating
centrosymmetric R22(8) and R44(16) rings.
The only other example in this series of a sheet of alter-
nating R22(8) and R66(32) rings built from N—Hꢀ ꢀ ꢀN and N—
Hꢀ ꢀ ꢀO hydrogen bonds, as in (I) and (II), was found in the
structure of (V). This differs from (I) and (II), both in
adopting a type A conformation and in the constitution of the
NR2 group bonded to C6. This substituent contains an N—H
bond that forms an intramolecular N—Hꢀ ꢀ ꢀO hydrogen bond
to the formyl O atom but otherwise plays no role in the
supramolecular aggregation.
Compound (II)
Crystal data
3
˚
V = 1327.1 (8) A
Z = 4
C13H13ClN4O2
Mr = 292.72
Monoclinic, P21=n
Mo Kꢂ radiation
ꢃ = 0.30 mmꢂ1
T = 120 (2) K
0.27 ꢄ 0.15 ꢄ 0.10 mm
˚
a = 11.301 (4) A
˚
b = 8.642 (3) A
˚
c = 14.568 (5) A
ꢁ = 111.13 (3)ꢁ
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.939, Tmax = 0.971
18363 measured reflections
3028 independent reflections
2010 reflections with I > 2ꢄ(I)
Rint = 0.103
Refinement
R[F2 > 2ꢄ(F2)] = 0.061
wR(F2) = 0.143
S = 1.11
183 parameters
H-atom parameteꢂrs3 constrained
˚
Áꢅmax = 0.52 e A
ꢂ3
˚
3028 reflections
Áꢅmin = ꢂ0.43 e A
All H atoms were located in difference maps and then treated as
˚
riding atoms, with C—H distances of 0.95 (aromatic) or 0.98 A
˚
(methyl) and N—H distances of 0.88 A, and with Uiso(H) =
Experimental
kUeq(carrier), where k = 1.5 for the methyl groups and k = 1.2 for all
other H atoms.
A solution containing 1 mmol of each of 2-amino-4,6-dichloro-5-
formylpyrimidine, the appropriate secondary amine [methyl(2-
methylphenyl)amine for (I) and methyl(2-methoxyphenyl)amine for
(II)] and triethylamine as a base, in ethanol (5 ml), was heated under
reflux for 3 h. The mixtures were cooled to ambient temperature and
the resulting solid products were collected by filtration, washed with
cold ethanol and dried in air before being recrystallized from ethanol
to give yellow crystals of (I) and (II) suitable for single-crystal X-ray
diffraction. Compound (I) (yield 80%, m.p. 456–458 K): MS (70 eV)
m/z (%) 278/276 (M + 2/M+, 13/42), 261/260 (55/17), 259 (100),
212 (13), 198 (23), 129/128 (31/8), 92/91 (6/20); HR–MS calculated for
C13H13ClN4O: 276.0778, found 276.0780. Compound (II) (yield 81%,
m.p. 454–456 K): MS (70 eV) m/z (%) 294/292 (M + 2/M+, 7/21), 263/
261 (35/100), 234/233 (4/11), 131/129 (8/21); HR–MS calculated for
C13H13ClN4O2 292.0727, found 292.0727.
For both compounds, data collection: COLLECT (Hooft, 1999);
cell refinement: DIRAX/LSQ (Duisenberg et al., 2000); data reduc-
tion: EVALCCD (Duisenberg et al., 2003); program(s) used to solve
structure: SIR2004 (Burla et al., 2005); program(s) used to refine
structure: OSCAIL (McArdle, 2003) and SHELXL97 (Sheldrick,
2008); molecular graphics: PLATON (Spek, 2003); software used to
Table 1
Selected geometric parameters (A, ) for (I) and (II).
ꢁ
˚
(a) Selected distances and angles.
(I)
(II)
N1—C2
C2—N3
N3—C4
C4—C5
C5—C6
C6—N1
C2—N2
C5—C51
C51—O51
C6—N61
1.331 (3)
1.355 (3)
1.307 (3)
1.382 (4)
1.437 (3)
1.328 (3)
1.320 (3)
1.460 (4)
1.212 (3)
1.351 (3)
1.336 (4)
1.342 (4)
1.314 (4)
1.387 (4)
1.425 (4)
1.328 (4)
1.322 (4)
1.461 (4)
1.208 (4)
1.369 (4)
Compound (I)
Crystal data
3
˚
C13H13ClN4O
Mr = 276.72
V = 1284.75 (19) A
Z = 4
Mo Kꢂ radiation
ꢃ = 0.30 mmꢂ1
T = 120 (2) K
Monoclinic, P21=n
˚
a = 11.1502 (8) A
˚
b = 8.7271 (8) A
C61—C62—O62
C63—C62—O62
–
–
115.3 (3)
125.1 (3)
˚
c = 13.7129 (13) A
0.47 ꢄ 0.37 ꢄ 0.26 mm
ꢁ = 105.676 (7)ꢁ
C4—C5—C51—O51
N1—C6—N61—C61
C6—N61—C61—C62
C61—C62—O62—C68
N1—C6—N61—C67
24.5 (4)
ꢂ150.2 (2)
52.9 (3)
–
20.8 (5)
ꢂ145.5 (3)
51.2 (4)
Data collection
ꢂ176.3 (3)
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.874, Tmax = 0.927
23784 measured reflections
2946 independent reflections
1999 reflections with I > 2ꢄ(I)
Rint = 0.059
7.4 (3)
3.1 (4)
(b) Substituent-atom deviations from the pyrimidine plane.
Atom
(I)
(II)
Refinement
N2
ꢂ0.093 (2)
0.106 (2)
ꢂ0.368 (2)
0.218 (2)
0.118 (2)
ꢂ0.125 (3)
0.106 (2)
ꢂ0.402 (3)
0.331 (2)
0.085 (2)
Cl4
C51
O51
N61
R[F2 > 2ꢄ(F2)] = 0.051
wR(F2) = 0.155
S = 1.14
174 parameters
H-atom parameteꢂrs3 constrained
˚
Áꢅmax = 0.38 e A
ꢂ3
˚
2946 reflections
Áꢅmin = ꢂ0.46 e A
Acta Cryst. (2009). C65, o11–o14

organic compounds
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.
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem.
Int. Ed. Engl. 34, 1555–1573.
Brammer, L., Bruton, E. A. & Sherwood, P. (2001). Cryst. Growth Des. 1, 277–
290.
Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., De
Caro, L., Giacovazzo, C., Polidori, G. & Spagna, R. (2005). J. Appl. Cryst. 38,
381–388.
Cobo, J., Trilleras, J., Quiroga, J., Marchal, A., Nogueras, M., Low, J. N. &
Glidewell, C. (2008). Acta Cryst. B64, 596–609.
Table 2
Hydrogen bonds and short intermolecular contacts (A, ) for (I) and (II).
ꢁ
˚
Compound
(I)
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
N2—H21ꢀ ꢀ ꢀO51i
N2—H21ꢀ ꢀ ꢀCl1i
N2—H22ꢀ ꢀ ꢀN3ii
0.88
0.88
0.88
2.38
2.58
2.11
3.052 (3)
3.377 (2)
2.988 (3)
134
152
171
(II)
N2—H21ꢀ ꢀ ꢀO51i
N2—H21ꢀ ꢀ ꢀCl1i
N2—H22ꢀ ꢀ ꢀN3ii
0.88
0.88
0.88
2.55
2.58
2.12
3.125 (4)
3.375 (3)
2.983 (4)
124
150
168
Duisenberg, A. J. M., Hooft, R. W. W., Schreurs, A. M. M. & Kroon, J. (2000).
J. Appl. Cryst. 33, 893–898.
Duisenberg, A. J. M., Kroon-Batenburg, L. M. J. & Schreurs, A. M. M. (2003).
J. Appl. Cryst. 36, 220–229.
Symmetry codes: (i) x ꢂ 12 ; ꢂy þ 12 ; z ꢂ ; (ii) ꢂx; ꢂy; ꢂz þ 1.
1
2
Ferguson, G. (1999). PRPKAPPA. University of Guelph, Canada.
Hooft, R. W. W. (1999). COLLECT. Nonius BV, Delft, The Netherlands.
Low, J. N., Trilleras, J., Cobo, J., Marchal, A. & Glidewell, C. (2007). Acta Cryst.
C63, o681–o684.
prepare material for publication: SHELXL97 and PRPKAPPA
(Ferguson, 1999).
McArdle, P. (2003). OSCAIL for Windows. Version 10. Crystallography
Centre, Chemistry Department, NUI Galway, Ireland.
Melguizo, M., Quesada, A., Low, J. N. & Glidewell, C. (2003). Acta Cryst. B59,
263–276.
Quesada, A., Marchal, A., Low, J. N. & Glidewell, C. (2003). Acta Cryst. C59,
o102–o104.
´
We thank ‘Servicios Tecnicos de Investigacion of Univer-
sidad de Jaen’ and the staff for data collection. JC thanks the
´
´
´
´
Consejerıa de Innovacion, Ciencia y Empresa (Junta de
´
´
Andalucıa, Spain) and the Universidad de Jaen for financial
support. JT and JQ thank COLCIENCIAS and UNIVALLE
(Universidad del Valle, Colombia) for financial support.
Quesada, A., Marchal, A., Melguizo, M., Low, J. N. & Glidewell, C. (2004).
Acta Cryst. B60, 76–89.
´
Quiroga, J., Trilleras, J., Insuasty, B., Abonıa, R., Nogueras, M., Marchal, A. &
Cobo, J. (2008). Tetrahedron Lett. 49, 3257–3259.
Seela, F. & Sterker, H. (1986). Helv. Chim. Acta, 69, 1602–1613.
Sheldrick, G. M. (2003). SADABS. Version 2.10. University of Gottingen,
Germany.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3279). Services for accessing these data are
described at the back of the journal.
¨
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13.
Taylor, E. C. & Gillespie, P. (1992). J. Org. Chem. 57, 5757–5761.
Thallapally, P. K. & Nangia, A. (2001). CrystEngComm, 3, 114–119.
Trilleras, J., Quiroga, J., Low, J. N., Cobo, J. & Glidewell, C. (2007). Acta Cryst.
C63, o758–o760.
References
´ ´
Aakeroy, C. B., Evans, T. A., Seddon, K. R. & Palinko, I. (1999). New J. Chem.
¨
pp. 145–152.
ꢃ
o14 Trilleras et al.
C13H13ClN4O and C13H13ClN4O2
Acta Cryst. (2009). C65, o11–o14