2-Amino-4-chloro-6-[N-methyl-N-(4-methylphenyl)amino]pyrimidine: Formation versus fragmentation of hydrogen-bonded chains of edge-fused R2 2(8) rings in 4,6-disubstituted 2-amino-pyrimidines

Article abstract of DOI:10.1107/S0108270108016405

Mol-ecules of the title compound, C12H13ClN4, are linked by two independent N - H...N hydrogen bonds into a chain of edge-fused R 2 ²(8) rings. The significance of this study lies in its attempt to rationalize the patterns of supra-molecular aggregation in the title compound and in a range of analogous 4,6-disubstituted 2-amino-pyrimidines.

Full text of DOI:10.1107/S0108270108016405

organic compounds
1
2
ring atoms N1 and N3 in the molecules at (ꢁx + 1, y ꢁ , ꢁz + 32 )
Acta Crystallographica Section C
Crystal Structure
Communications
1
2
3
2
and (ꢁx + 1, y + , ꢁz + ), respectively, so that molecules
related by the 21 screw axis along (12, y, ) are linked into a
3
4
ISSN 0108-2701
C(4)C(4)[R22(8)] chain of rings (Bernstein et al., 1995) (Fig. 2).
In addition, aryl atoms C63 in the molecules at (x, y, z) and
1
3
(ꢁx + 1, y + , ꢁz + ) act as hydrogen-bond donors, respec-
2
2
2-Amino-4-chloro-6-[N-methyl-
N-(4-methylphenyl)amino]pyrimidine:
formation versus fragmentation of
tively, to the pyrimidine rings of the molecules at (ꢁx, ꢁy + 1,
3
1
ꢁz + 1) and (x + 1, ꢁy + , z + ), which are themselves
2
2
components of the chains of rings along (ꢁ , ꢁy, 14 ) and (23, ꢁy,
1
2
54 ), respectively. Hence, the C—Hꢀ ꢀ ꢀꢀ(pyrimidine) hydrogen
hydrogen-bonded chains of edge-fused bond links the chains of rings parallel to [010] into a sheet
R22(8) rings in 4,6-disubstituted 2-amino-
parallel to (102).
pyrimidines
a
a
a
´
Ricaurte Rodrıguez, ‡ Manuel Nogueras, Justo Cobo,
John N. Lowb and Christopher Glidewellc*
a
´
´
´
´
Departamento de Quımica Inorganica y Organica, Universidad de Jaen, 23071
Jaen, Spain, bDepartment of Chemistry, University of Aberdeen, Meston Walk, Old
´
Aberdeen AB24 3UE, Scotland, and cSchool of Chemistry, University of St Andrews,
Fife KY16 9ST, Scotland
Correspondence e-mail: cg@st-andrews.ac.uk
Received 29 May 2008
Accepted 29 May 2008
Online 14 June 2008
Molecules of the title compound, C12H13ClN4, are linked by
two independent N—Hꢀ ꢀ ꢀN hydrogen bonds into a chain of
edge-fused R22(8) rings. The significance of this study lies in its
attempt to rationalize the patterns of supramolecular
aggregation in the title compound and in a range of analogous
4,6-disubstituted 2-aminopyrimidines.
Comment
In recent years, we have reported the molecular and supra-
molecular structures of a number of 4,6-disubstituted
2-aminopyrimidines (Low et al., 2002; Bowes et al., 2003;
Glidewell et al., 2003; Melguizo et al., 2003; Quesada et al.,
2002, 2004), which have proven to exhibit a very wide range of
supramolecular aggregation patterns. We report here the
structure of the title compound, (I) (Fig. 1), and we attempt a
simple rationalization of some of the structural themes
observed in earlier determinations. For the preparation of (I),
which is intended for eventual use as an intermediate in the
synthesis of a variety of fused heterocyclic derivatives, a
solvent-free fusion method was used for the selective mono-
substitution by N-methyl-4-toluidine of the 6-chloro substi-
tuent in the precursor compound 2-amino-4,6-dichloropyrim-
idine.
The formation of edge-fused chains of R22(8) as found in (I)
occurs in a number of other simple 2-aminopyrimidines, but
the disruption of such a chain formation appears to be readily
accomplished, resulting either from steric factors arising from
bulky substituents or from the presence of an alternative
hydrogen-bond acceptor which can compete effectively with
the pyrimidine ring N atoms. Chains of edge-fused R22(8) rings
that are topologically identical to that in (I) are found both in
The molecules of (I) are linked into sheets by a combination
of two independent N—Hꢀ ꢀ ꢀN hydrogen bonds and one C—
Hꢀ ꢀ ꢀꢀ(pyrimidine) hydrogen bond (Table 1). Amino atom N2
in the molecule at (x, y, z) acts as a hydrogen-bond donor to
‡ Permanent address: Department of Chemistry, Universidad Nacional de
´
Colombia, Bogota, AA 14490, Colombia.
o376 # 2008 International Union of Crystallography
doi:10.1107/S0108270108016405
Acta Cryst. (2008). C64, o376–o378

organic compounds
the symmetrically disubstituted aminopyrimidines (II) and
(III) (Low et al., 2002) and in the unsymmetrically substituted
compounds (IV) (Glidewell et al., 2003) and (V) (Melguizo et
al., 2003), although the different space groups and Z0 values
mean that different symmetry operations relate the molecules
within the chains.
However, in the structures of the related compounds (VI)–
(IX), it is possible to discern only small fragments of a chain of
edge-fused rings built from N—Hꢀ ꢀ ꢀN hydrogen bonds. Thus,
in (VI), whose constitution is similar to that of (III), the N—
Hꢀ ꢀ ꢀN hydrogen bonds generate only a centrosymmetric
R22(8) dimer, i.e. a two-molecule fragment of the chain found in
(I)–(V), and only one of the N—H bonds in (VI) is active in
hydrogen-bond formation, although the dimers are further
linked by a single C—Hꢀ ꢀ ꢀꢀ(pyrimidine) interaction (Ques-
ada et al., 2004). Compound (VII) crystallizes with Z0 = 2 in the
space group P21/c, and three independent N—Hꢀ ꢀ ꢀN
hydrogen bonds form an aggregate containing three edge-
fused R22(8) rings, i.e. a four-molecule fragment of the chain,
with again one of the N—H bonds playing no role in the
hydrogen bonding (Bowes et al., 2003). The morpholino
analogue of (VII), viz. compound (VIII), crystallizes in two
polymorphic forms, both in P21/c, with Z0 = 1 and 2 (Bowes et
al., 2003). In each polymorph, paired N—Hꢀ ꢀ ꢀN hydrogen
bonds generate a two-component R22(8) fragment, and these
are linked by N—Hꢀ ꢀ ꢀO hydrogen bonds to form sheets of
R22(8) and R66(40) rings in the Z0 = 1 form, and chains of
alternating R22(8) and R44(18) rings in the Z0 = 2 form. Hence,
all of the N—H bonds are active in hydrogen-bond formation
here. Entirely analogous behaviour is exhibited by (IX), which
is closely related to (II); paired N—Hꢀ ꢀ ꢀN hydrogen bonds
form an R22(8) dimer, again a two-molecule component of the
chain found in (I)–(V), and N—Hꢀ ꢀ ꢀO hydrogen bonds link
these dimers into a chain of alternating R22(8) and R44(16) rings
(Quesada et al., 2002).
The disruption of the chain formation in (VIII) and (IX)
can be interpreted straightforwardly in terms of the effective
competition by the more electronegative O atoms as
hydrogen-bond acceptors, leading to the replacement of some
of the N—Hꢀ ꢀ ꢀN hydrogen bonds by N—Hꢀ ꢀ ꢀO hydrogen
bonds. A more subtle question arises from the structural
differences between (II) and (IX), where precisely the same
sets of potential hydrogen-bond acceptors are present,
arranged with the same relative dispositions; the original
report on the structure of (IX), where the molecule has no
internal symmetry in the crystal (Quesada et al., 2002),
emphasized the interplay between the conformations adopted
by the benzyl substituents and the hydrogen-bond formation
as a significant determinant of the overall crystal structure.
The short-fragment formation by (VI) is readily understood in
terms of steric factors, but a significant anomaly is apparent in
the structure of (VII), where any steric factors might have
been expected to be significantly less than those in (V).
However, (VII) is in fact isomorphous and almost isostruc-
tural with the Z0 = 2 polymorph of (VIII) (Bowes et al., 2003)
and it is entirely possible that a Z0 = 1 polymorph of (VII)
having a different overall aggregation pattern could also
exist.
Figure 1
The molecular structure of (I), showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 30% probability level.
Experimental
A mixture of 2-amino-4,6-dichloropyrimidine (1.037 mmol) and
N-methyl-4-toluidine (1.815 mmol) was placed in a test tube and
heated at 473–483 K in an oil bath for 35 min. The reaction mixture
was cooled to ambient temperature and the resulting solid was
washed with an excess of a saturated aqueous solution of sodium
hydrogen carbonate. The crude product was collected by filtration,
washed successively with water and diethyl ether, and then dried in
an oven at 333 K to give the title compound. Crystals suitable for
single-crystal X-ray diffraction were obtained by slow evaporation of
a solution in dimethyl sulfoxide (yield 92%, m.p. 473–475 K). HRMS:
found 248.0822; C12H1335ClN4 requires: 248.0829.
Figure 2
A stereoview of part of the crystal structure of (I), showing the formation
of a hydrogen-bonded chain of edge-fused rings parallel to the [010]
direction.
ꢂ
´
Acta Cryst. (2008). C64, o376–o378
Rodrıguez et al. C12H13ClN4 o377

organic compounds
Crystal data
graphics: PLATON (Spek, 2003); software used to prepare material
for publication: SHELXL97 and PRPKAPPA (Ferguson, 1999).
3
˚
V = 1183.57 (17) A
Z = 4
C12H13ClN4
Mr = 248.71
Monoclinic, P21=c
Mo Kꢂ radiation
ꢃ = 0.30 mmꢁ1
T = 120 (2) K
0.41 ꢄ 0.25 ꢄ 0.22 mm
´
´
The authors thank ‘Servicios Tecnicos de Investigacion of
Universidad de Jaen’ and the staff for data collection. MN and
˚
a = 9.8184 (5) A
´
˚
b = 7.8683 (7) A
˚
c = 15.5719 (16) A
´
´
JC thank the Consejerıa de Innovacion, Ciencia y Empresa
ꢁ = 100.309 (7)ꢃ
´
´
(Junta de Andalucıa, Spain) and Universidad de Jaen for
financial support. RR thanks COLCIENCIAS and Univer-
sidad Nacional de Colombia for financial support, and
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.885, Tmax = 0.936
29284 measured reflections
2720 independent reflections
1933 reflections with I > 2ꢄ(I)
Rint = 0.058
´
Fundacion Carolina for a fellowship to carry out postgraduate
studies at Universidad de Jaen.
´
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3241). Services for accessing these data are
described at the back of the journal.
Refinement
R[F2 > 2ꢄ(F2)] = 0.048
wR(F2) = 0.128
S = 1.10
156 parameters
H-atom parameteꢁrs3 constrained
References
˚
Áꢅmax = 0.44 e A
ꢁ3
˚
2720 reflections
Áꢅmin = ꢁ0.30 e A
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Hydrogen-bond geometry (A, ).
ꢃ
˚
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N2—H2Aꢀ ꢀ ꢀN3i
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0.88
0.88
0.95
2.29
2.47
2.68
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1
2
3
2
1
2
3
2
Symmetry codes: (i) ꢁx þ 1; y þ ; ꢁz þ ; (ii) ꢁx þ 1; y ꢁ ; ꢁz þ ; (iii) ꢁx; ꢁy þ 1,
ꢁz þ 1.
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˚
˚
pyrimidine) or 0.98 A (CH3) and N—H distances of 0.88 A, and with
Uiso(H) = kUeq(carrier), where k = 1.5 for the methyl groups and k =
1.2 for all other H atoms.
´
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o378 Rodrıguez et al. C12H13ClN4
Acta Cryst. (2008). C64, o376–o378