8
18
J Chem Crystallogr (2007) 37:817–824
2
-yl)amine (2) were prepared by adding a solution of 2,4-
dichloro-6-methylpyrimidine (0.65 g, 4.0 mmol) in THF
5 mL) to benzylamine (0.86 g, 8 mmol, 2 eq). The resulting
(
solution was stirred at 30 ꢁC for 18 h, filtered and concen-
trated in vacuo. The residue was purified by flash
chromatography using 1:9 ethyl acetate–hexanes to yield the
corresponding isomers. Slow evaporation of the eluting sol-
vents allowed crystal formation.
1
(
1) yield 340 mg, 49%, mp 78–81 ꢁC; H NMR
Scheme 1 Chemical structures for (1) and (2)
(
CDCl ): d 2.25 (s, 3H), 4.51 (d, 2H), 6.06 (s, 1H),
.15 (br s, 1H), 7.29 (m, 5H) ppm; C NMR (CDCl ): d
3
1
3
6
2
1
3
3.1, 44.9, 99.9 (br), 126.7, 127.1, 128.3, 136.8, 159.6,
63.8, 171.1 (br) ppm.
1
(
2) yield 142 mg, 19%, mp 136–138 ꢁC; H NMR
(
CDCl ): d 2.29 (s, 3H), 4.64 (s, 2H), 5.48 (br s, 1H),
.48 (s, 1H), 7.31 (m, 5H) ppm; C NMR (CDCl ): d
3
1
3
6
2
1
3
3.2, 44.9, 109.0, 126.7, 126.9, 128.0, 139.2, 160.7,
61.6, 169.0 ppm.
X-ray Crystallography
Intensity data for colorless crystals of (1)Á0.5H O and (2)
2
were collected at 150 K on a Bruker SMART 1000 CCD
fitted with Mo Ka radiation. The data sets were corrected
for absorption based on multiple scans [4] and reduced
using standard methods [5]. The structures was solved by
direct-methods [6] and refined by a full-matrix least-
Fig. 1 Illustrative example of a high-energy conformer of (1), left,
and (2), right
2
squares procedure on F with anisotropic displacement
parameters for non-hydrogen atoms, carbon-and nitrogen-
low-energy conformers; Fig. 1 highlights the high-energy
conformer of 1 which is responsible for line broadening
and also the high energy conformer of 2 which does not
induce this effect. Aniline derivatives have been shown to
prefer a stable orientation orthogonal to the plane of the
pyrimidine residue and consequently no line broadening
would be observed [3]. This is in keeping with our mod-
eling data with conformational energy differences of the
bound hydrogen atoms in their calculated positions and a
2
2
2
weighting scheme of the form w = 1/[r (F ) + (aP) + bP]
o
2
o
2
c
where P = (F + 2F )/3) [7]. Crystal data and refinement
details are given in Table 1. Figures 2 and 5, showing the
atom labeling schemes, were drawn with 50% displace-
ment ellipsoids using ORTEP [8] and the remaining figures
were drawn with DIAMOND [9] and Qmol (Figs. 2 and 5)
[10]. Data manipulation and interpretation were accom-
plished using teXsan [11] and PLATON [12].
–
1
order of *2 kJ mol between the highest and lowest
energy conformer. In order to confirm our experimental
and theoretical observations, the crystal and molecular
structures of the two representative compounds, benzyl-(2-
chloro-6-methylpyrimidin-4-yl)amine (1), characterized as
a hemihydrate, and benzyl-(4-chloro-6-methylpyrimidin-
Results and Discussion
2
-yl)amine (2) were determined.
The crystallographic asymmetric unit of (1)Á0.5H O com-
2
prises two independent molecules of (1) and a solvent
water molecule of crystallization. The molecular structures
of (1) are illustrated in Fig. 2 and selected geometric
parameters are collected in Table 2. Immediately apparent
from Fig. 2 is that there are conformational differences
between the two molecules in relation to the orientation of
the benzyl residue with respect to the remaining part of the
molecule so that in the first independent molecule, the
Experimental
Synthesis
The isomeric compounds benzyl-(2-chloro-6-methylpyrimi-
din-4-yl)amine (1) and benzyl-(4-chloro-6-methylpyrimidin-
1
23
Odell, Luke R.
