Synthesis and crystal structure of 3,5-dichloro-6-morpholinopyridin-2-ol

Article abstract of DOI:10.1007/s10870-009-9592-2

A new compound having potential bioactivities 3,5-dichloro-6- morpholinopyridin-2-ol (1) was synthesized and characterized by single crystal X-diffraction. The crystal is monoclinic, space group P2₁/c with a = 10.3609 (6), b = 10.5711 (7), c = 10.3190 (5) A, β = 108.9433 (15)°, V = 1068.99 (11) A³, Z = 4, C₉H ₁₀Cl₂N₂O₂, D _c = 1.548 g/cm³, μ (MoKα) = 0.71075 A, S = 1.01, F (000) = 512.00, R = 0.0397 and wR = 0.1364. In the unit cell, there are two independent molecules linked by intermolecular O-H???O (2.693(2) A) hydrogen bonds forming onedimensional expanded structure. Graphical Abstract: As part of our ongoing research work on pyridine derivatives, the title compound crystal structure is important to study the relationship between the structure and its biological activities, thus it is urgent to publish in time.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-009-9592-2

J Chem Crystallogr (2009) 39:919–922
DOI 10.1007/s10870-009-9592-2
ORIGINAL PAPER
Synthesis and Crystal Structure of 3,5-Dichloro-6-
morpholinopyridin-2-ol
Hui Zheng Æ Yun-kui Liu Æ Chao Shen Æ
Zhen-yuan Xu
Received: 12 January 2009 / Accepted: 7 June 2009 / Published online: 19 June 2009
Ó Springer Science+Business Media, LLC 2009
Abstract A new compound having potential bioactivities
3,5-dichloro-6-morpholinopyridin-2-ol (1) was synthesized
and characterized by single crystal X-diffraction. The crystal
is monoclinic, space group P21/c with a = 10.3609 (6),
study the relationship between the structure and its bio-
logical activities, a few related single crystals were pre-
pared [7]. As part of our work, we herein present the crystal
structure of the title compound, in which an interesting
intermolecular O–HÁÁÁO hydrogen bond linking two inde-
pendent molecules to form one-dimensional expanded
structure in the unit cell was found.
˚
b = 10.5711 (7), c = 10.3190 (5) A, b = 108.9433 (15)°,
3
V = 1068.99 (11) A , Z = 4, C9H10Cl2N2O2, Dc = 1.548
˚
3
˚
g/cm , l (MoKa) = 0.71075 A, S = 1.01, F (000) =
512.00, R = 0.0397 and wR = 0.1364. In the unit cell, there
are two independent molecules linked by intermolecular
˚
O–HÁÁÁO (2.693(2) A) hydrogen bonds forming onedimen-
Experimental
sional expanded structure.
Reagents and Apparatus
Keywords Pyridine heterocyclic compounds Á
Hydrogen bond Á Synthesis Á Crystal structure
All the reagents were purchased commercially and used
without further purification. The melting point was deter-
mined using a XT-4 melting-point apparatus and uncor-
rected. IR spectra were recorded on a Bruker Equinox-55
spectrophotometer using KBr discs in the 4,000–400 cm-1
Introduction
The title compound belongs to the family of pyridine het-
erocyclic derivatives, which have attracted much attention
for their biological activities such as anti-virus, herbicidal,
pesticidal and plant growth regulating activity etc. [1–3].
As part of our ongoing investigation of heterocyclic pes-
ticides [4, 5], the title compound (1) has recently been
prepared in our laboratory, which serves as the key inter-
mediate for preparation of 3,5-dichloro-6-morpholinopyr-
idin-2-yl diethyl thiophosphate (Fig. 1) [6]. In order to
1
region. The H NMR and 13C NMR spectra were obtained
on a Bruker AC-500 (500 MHz) instrument in CDCl3 using
TMS as internal standard. Chemical shifts (d) are expressed
in ppm and coupling constants J are given in Hz. Mass
H. Zheng Á C. Shen
College of Material, Chemistry & Chemical Engineering,
Hangzhou Normal University, 310036 Hangzhou, China
Y. Liu Á Z. Xu (&)
College of Chemical Engineering & Materials, Zhejiang
University of Technology, 310014 Hangzhou, China
e-mail: zhenghui86@gmail.com; zhenghui86@tom.com
Fig. 1 The synthesis of title compound
123

920
J Chem Crystallogr (2009) 39:919–922
Synthesis of the Title Compound
spectra were obtained on a Agilent 5973N mass spec-
trometer. The crystal data of the title compound were
collected on Rigaku RAXIS-RAPID X-ray single crystal
diffractometer.
The title compound was synthesized according to the
general procedure of the patent [8]. The single crystals
suitable for determination were obtained by slow evapo-
ration of the solution of the title compound dissolved in a
mixture of ether: dichloromethane = 3:1 at room temper-
ature. M. p: 157–159 °C. IR (KBr, vmax/cm-1): 3058, 2967,
2848, 1649, 1576, 1442, 1376, 1341, 1299, 1271, 1161,
1113 1078. 1H NMR (CDCl3, 500 MHz) d: 3.32 (t,
J = 5.0 Hz, 4H), 3.77 (t, J = 4.5 Hz, 4H), 7.48 (s, 1H),
10.93 (s, 1H). 13C NMR (CDCl3, 125 MHz) d: 49.24,
66.79, 100.40, 106.08, 141.95, 150.38, 157.52. MS (70 eV)
(m/z): 248 (M?).
Table 1 Crystal data and structure refinement
Chemical formula
CCDC deposit no.
Color
C9H10Cl2N2O2
CCDC 672267
Colorless
Crystal dimensions (mm)
Formula weight
Crystal system
0.38 9 0.29 9 0.14
249.10
Monoclinic
P21/c
Space group
X-ray Crystallography
Unit cell dimensions
˚
a (A)
10.3609 (6)
10.5711 (7)
10.3190 (5)
108.9433 (15)
1068.99 (11)
4
˚
b (A)
A colorless parellepiped crystal having approximate
dimensions of 0.38 mm 9 0.29 mm 9 0.14 mm was
selected and the data collection was carried out on a Rig-
aku RAXIS RAPID Imaging Plate area detector equipped
˚
c (A)
b (°)
3
V (A )
˚
˚
with a Mo-Ka (k = 0.71075 A) radiation. The data were
Z
Density (calculated, g/cm3)
Absorption coefficient (mm-1
Radiation
1.548
collected at 296 (1) K to a maximum 2h value of 54.86°. A
sweep of the data was done by using an x scan with 5°
oscillation. A total of the 2,439 reflections were unique
(Rint = 0.024) and 2081 observed (I [ 2r(I)). The linear
)
0.587
˚
MoKa (k = 0.71075 A)
3.1–27.4
Theta min–max (°)
Reflections collected/unique
Range of h, k, l
absorption coefficient for Mo-Ka radiation is 0.587 mm-1
.
2,439/2,018
An empirical absorption correction was adopted, resulting
in the transmission factors ranging from 0.72 to 0.92. The
data were corrected for Lorenz-polarization factors.
The structure was solved by direct methods (SIR97) [9]
and expanded with Fourier techniques (DIRDIF99) [10].
The non-hydrogen atoms were refined anisotropically, and
-13:12, -13:0, 0:13
1.012
Goodness-of-fit on F2
R indices
3
Largest feature (e/A )
R = 0.0397 and wR = 0.1364.
0.39 and -0.33
296 (1)
˚
Temperature (K)
Table 2 The selected bond
˚
Cl1–C1
C3–C4
C6–C7
O1–C4
O2–C7
N1–C4
N1–C5
N2–C5
N2–C9
C1–C2
C1–C5
Cl2–C3
O2–C8
C2–C3
N2–C6
C8–C9
C1–C2
1.736(2)
1.392(2)
1.513(3)
1.341(2)
1.441(3)
1.332(2)
1.344(2)
1.403(2)
1.470(3)
1.385(2)
1.396(2)
1.7267(19)
1.441(2)
1.373(3)
1.462(2)
1.506(3)
1.385(2)
C7–O2–C8
C4–N1–C5
C5–N2–C6
C6–N2–C9
Cl1–C1–C2
C2–C1–C5
C1–C2–C3
C2–C3–C4
O1–C4–N1
O1–C4–C3
N1–C4–C3
N1–C5–N2
N1–C5–C1
N2–C5–C1
N2–C6–C7
O2–C7–C6
O2–C8–C9
110.70(16)
119.61(17)
118.08(19)
110.26(17)
118.66(16)
119.9(2)
C7–O2–C8–C9
C8–O2–C7–C6
C4–N1–C5–N2
C4–N1–C5–C1
C5–N1–C4–O1
C5–N2–C6–C7
C6–N2–C5–N1
C6–N2–C5–C1
C5–N2–C9–C8
C9–N2–C5–N1
C9–N2–C5–C1
C6–N2–C9–C8
C9–N2–C6–C7
C2–C1–C5–N1
C2–C1–C5–N2
C5–C1–C2–C3
C2–C3–C4–O1
-56.3(2)
57.2(2)
lengths (A), bond angles (°) and
torsion angles (°) data
175.7(2)
-0.0(2)
179.5(2)
-161.1(2)
-20.4(3)
155.4(2)
161.16(18)
115.1(2)
-69.2(2)
-60.1(2)
60.6(2)
118.71(19)
118.91(18)
119.34(18)
118.33(17)
122.3(2)
118.57(17)
120.51(17)
120.78(19)
107.8(2)
0.5(3)
-175.1(2)
0.3(3)
111.4(2)
111.6(2)
-178.7(2)
123

J Chem Crystallogr (2009) 39:919–922
921
Fig. 2 Molecular structure of
the title compound with 50%
thermal ellipsoids. Dashed lines
indicate hydrogen bonds.
Symmetry codes: (i) –x ? 1,
y ? 1/2, -z ? 1/2
concept of a smaller covalent radius for a Csp2 atom than
for a Csp3 atom. The interesting feature lies in that the
2-position C–O bond on pyridine ring adopts an enol form
rather than a keto form. Thus in the unit cell, the hydroxy
group of one molecule could form intermolecular hydrogen
˚
Table 3 Hydrogen bond lengths (A) and bond angles (°)
D–HÁÁÁA
d (DÁÁÁH)
d (HÁÁÁA)
d (DÁÁÁA)
\(DHA)
O1–H101–O2
2.693(2)
0.892
1.809
170.7
Symmetry codes: (i) –x ? 1, y ? 1/2, -z ? 1/2
˚
bond O1–H101ÁÁÁO2 (2.693(2) A) with the oxygen atom on
morpholine ring of another molecule and such hydrogen
bonds could expand infinitely along the b axes direction,
forming one-dimensional structure (Fig. 2).
the hydrogen atoms were placed in the calculated positions
and refined with the riding model with Uiso(H) = 1.2
Ueq(C). The final cycle of full-matrix least-squares refine-
ment on F2 based on 2,349 observed reflections and 137
variable parameters converged (largest parameter shift is
0.00 times its esd) with unweighted and weighted agree-
ment factors to R = 0.0397 and wR = 0.1364 (w = 1/
[0.0019F2o ? 5.0000\s(Fo2) ? 0.5000]/(4F2o). The maxi-
mum and minimum peaks on the final difference Fourier
Supplementary Material
CCDC 672267 contains the supplementary crystallographic
data for this paper. These data can be obtained free of
charge via (please use the link below) by e-mailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre 12 Union Road Cambridge
CB2 1EZ, UK. Fax: ?44(0)1223-336033.
3
˚
map correspond to 0.39 and -0.33 e/A , respectively.
S = 1.01 and (D/r)max = 0.0000. The neutral atom scat-
tering factors were taken from Cromer and Waber [11]. All
calculations were performed with Crystal Structure crys-
tallographic software package [12, 13].
Crystal and structure refinement data is shown in
Table 1. Selected bond lengths and bond angles are listed
in Table 2, and the hydrogen bond lengths and bond angles
in Table 3.
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The bond lengths and angles are in normal range (Table 2),
and in agreement with 3,5-dichloro-6-morpholinopyridin-
2-yl diethyl thiophosphate [6]. In the crystal structures, the
morpholine ring adopts a chair conformation with the C6–
N2–C9 angle of 110.26 (17)° and the C7–O2 distance of
˚
1.441(3) A (Table 2). The pyridine ring is almost planar
with the C4–N1–C5–C1 torsion angle of -0.0 (2)°. The
O1–C4 and N2–C5 bond length is significantly shorter than
normal O–C and N–C bond distances for the common
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