Synthesis and crystal structure of diisopropyl hydroxy(4-methoxyphenyl) methylphosphonate

Article abstract of DOI:10.1007/s10870-008-9386-y

The title compound, C₁₄H₂₃O₅P, was synthesized by the reaction of 4-methoxybenzaldehyde and diisopropyl phosphite. Its structure was determined with X-ray crystallographic, NMR, MS, and elemental analysis (EA) techniques.

Full text of DOI:10.1007/s10870-008-9386-y

J Chem Crystallogr (2008) 38:761–764
DOI 10.1007/s10870-008-9386-y
ORIGINAL PAPER
Synthesis and Crystal Structure of Diisopropyl Hydroxy
(4-methoxyphenyl)methylphosphonate
Hua Fang Æ Mei Juan Fang Æ Rui Zao Yi Æ
Yu Fen Zhao
Received: 20 September 2007 / Accepted: 27 March 2008 / Published online: 15 April 2008
Ó Springer Science+Business Media, LLC 2008
Abstract The title compound, C14H23O5P, was synthesized
by the reaction of 4-methoxybenzaldehyde and diisopropyl
phosphite. Its structure was determined with X-ray crystallo-
graphic, NMR, MS, and elemental analysis (EA) techniques.
The crystal belongs to monoclinic, space group P 21/n with the
Introduction
a-Hydroxyphosphonic acids and their esters exhibit a variety
of biological activities as enzyme inhibitors, antiviral, anti-
bacterial and anticancer drugs [1–4]. a-Hydroxyphosphonates
are easily synthesized from aldehydes and phosphites via the
base-catalyzed the Pudovik reaction [5]. This reaction mainly
proceeded in the presence of a basic catalyst [6, 7], acid cat-
alyst [8] or a metal fluoride [9]. Recently we carried out the
Pudovik reaction in 25% aqueous ammonia solution as a basic
catalyst and discovered that the reaction proceeds smoothly
under these conditions. In this paper we have synthesized a
new a-hydroxyphosphonate and report its crystal structure. In
this paper we report the X-ray structure of diisopropyl
hydroxy(4-methoxyphenyl)methylphosphonate and intermo-
lecular interactions.
˚
following crystallographic parameters: a = 10.529 (2) A,
˚
˚
b = 8.424 (2) A, c = 19.448 (4) A, a = 90°, b = 105.2
(3)°, c = 90°, l = 0.180 mm-1, V = 1664.1 (6) A , Z = 4,
3
˚
Dx = 1.207 mg/mm3, F (000) = 648, T = 293 (2) K,
2.00° B h B 25.50°. The final residual factor is 0.049 for
1933 reflections with I [ 2r (I). Crystal packing is stabilized
by interatomic hydrogen bond interactions between the dou-
bly bonded phosphoryl O atom and the hydroxyl H atom
which link the molecules into chains along the [011] plane of
the unit cell.
Keywords Synthesis ꢀ Crystal structure ꢀ
a-Hydroxyphosphonate
Experimental
Materials and Methods
The melting point was obtained uncorrected with a Yanco
micro melting point apparatus. Infrared-spectra were
recorded on a Nicolet AVATR 360 FTIR spectrophotom-
H. Fang ꢀ R. Z. Yi
The Third Institute of Oceanography of the State Oceanic
Administration, Xiamen 361005, People’s Republic of China
1
eter using KBr disks. H, 13C and 31P NMR spectra were
recorded on a Bruker 400 MHz spectrometer operating at
400, 100 and 160 MHz, respectively. The chemical shifts
were reported in ppm with respect to the references and
were stated relative to external tetramethylsilane (TMS) for
1H and 13C NMR, and to 85% phosphoric acid for 31P
NMR. Elemental analyses were performed with a Flash EA
1112. The mass spectrum was acquired with a Bruker
ESQUIRE-3000 plus ion trap spectrometer equipped with a
gas nebulizer probe in the positive ion mode.
M. J. Fang (&) ꢀ Y. F. Zhao
Department of Pharmaceutical Science, Medical College,
Xiamen University, Xiamen 361005, People’s Republic of China
e-mail: fangmj@xmu.edu.cn
Y. F. Zhao
Department of Chemistry, Key Laboratory for Chemical Biology
of Fujian Province, College of Chemistry and Chemical
Engineering, Xiamen University, Xiamen 361005, People’s
Republic of China
123

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J Chem Crystallogr (2008) 38:761–764
Scheme 1 Synthetic pathway
of diisopropyl hydroxy(4-
methoxyphenyl)methyl
phosphonate
O
O
25 % NH3 (aq)
THF, ice bath
O
HP(OiPr)2
+
O
P
H
O
O
O
OH
Synthesis of Diisopropyl Hydroxy(4-
methoxyphenyl)methylphosphonate
Table 1 Crystal data and structure refinement details
CCDC nos.
659487
14H23O5P
Empirical formula
Formula weight
C
To a solution of 4-methoxybenzaldehyde (5 mmol, 0.68 g)
and diisopropyl phosphite (5 mmol, 0.83 g) in tetrahydrofu-
ran (5 mL) at 0 °C was added aqueous ammonia (25%,
1.6 mL). The mixture was left to stand at ambient temperature
for 2 h, duringwhich time a precipitate separated (Scheme 1).
The precipitate was filtered off and washed rapidly with cold
diethyl ether [10]. Column chromatography of the solid using
silica gel and 20% ethyl acetate in petroleum ether solution
gave the title compound (C14H23O5P; 1.29 g in 85.4% yield.
302.29
Crystal system, space group
Unit cell dimensions
Monoclinic, P 21/n
˚
a = 10.529 (2) A
˚
b = 8.424 (2) A
˚
c = 19.448 (4) A
a = 90°
b = 105.2 (3)°
c = 90°
3
˚
1
Volume
1664.1 (6) A
m. p. 145–146 °C): H NMR (400 MHz, CDCl3) d (ppm):
7.43 (d, 2H, J = 4.2 Hz, ArH), 6.89 (d, 2H, J = 4.2 Hz,
Z, Calculated density
Density (calculated), mg/mm3
Absorption coefficient
F (000)
4, 1.207 mg/mm3
1
ArH), 4.90 (d, 1H, JP–CH = 5 Hz, CH), 4.65–4.60 (m, 2H,
1.207
0.180 mm-1
648
2OCH(CH3)2), 3.81 (s, 3H, OCH3), 3.72 (br, 1H, OH), 1.28–
1.14 (m, 12H, 2OCH(CH3)2); 13C NMR: 159.38, 128.93,
128.65, 128.59, 113.58, 113.56, 71.49 (d, 1JP–CH = 161 Hz,
CH), 71.83, 71.55 (2OCH(CH3)2), 55.25 (OCH3), 23.62,
23.90 24.09, 24.19; 31P NMR: 20.08; IR (KBr) t (cm-1):
3270, 1612, 1583, 1377; MS m/z: 303 [M + H]+, 605
[2M + H]+, 627[2M + Na]+; Anal. Calcd. forC14H23O5P:C
55.62, H 7.67; Found C 55.65, H 7.69. The colorless single
crystal was cultured from a mixture solution of dichloro-
methane/petroleum ether (v/v = 1/6) by slow evaporation at
room temperature.
Crystal size
0.20 9 0.18 9 0.13 mm3
Theta range for data collection
Limiting indices
2.00–25.50°
-10 B h B 12,
-10 B k B 10,
-23 B l B 22
Reflections collected
4896
Independent/observed reflections
Completeness to theta = 25.00
Refinement method
2897 [R(int) = 0.048]
93.3%
Full-matrix least-squares on F2
0.972 and 0.965
2897/0/186
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
Crystal Structure Determinations and Refinements
1.00
X-ray data on a single crystal of dimensions 0.20 mm 9
0.18 mm 9 0.13 mm was collected on a Bruker SMART
CCD X-ray area detector diffractometer at room tempera-
Final R indices (I [ 2sigma(I))
R indices (all data)
R1 = 0.049, wR2 = 0.102
R1 = 0.092, wR2 = 0.113
-3
˚
0.24 and -0.22 e A
Largest diff. peak and hole
˚
ture using Mo Ka radiation (k = 0.7173 A) with / and x
scans. An absorption correction was applied using SAD-
ABS 2001 [11]. The structures were solved by direct
methods using the SHELXL-97 program [12]. All H atoms
were placed in geometrically idealized positions and trea-
ted as riding on their parent atoms, with C–H = 0.93
Results and Discussion
The crystal data and final refinement details of the title com-
pound are given in Table 1, and the final geometrical
parameters are given in Table 2. Table 3 gives the bond dis-
tances and bond angles of non-hydrogen atoms, respectively.
The molecule consists of a phenyl ring at C(2). The average
˚
(aromatic), 0.96 (CH3) or 0.98 (CH), O–H = 0.82 A and
U
iso(H) = 1.2Ueq (aromatic C and CH) or 1.5Ueq (methyl
C and O). Anisotropic temperature factors were introduced
˚
value of the bond distances (1.380(3) A) and exocyclic bond
for all non-hydrogen atoms, and least-squares refinements
P
were carried out by minimizing w (jFoj - jFcj)2, where
Fo and Fc are the observed and calculated structure factors.
The full crystallographic details are deposited in CCDC
database under the reference number 659487 (see supple-
mentary material).
angles (120.0(3)°) in the phenyl ring have normal values as
compared to those of similar structure [13, 14]. The configu-
ration around the phosphorus atom, which is sp3 hybridized, is
that of a distorted tetrahedron with phosphorous at the center.
˚
The P–O bond lengths are P(1)–O(2) = 1.469 (2) A,
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J Chem Crystallogr (2008) 38:761–764
763
Table 2 Atomic coordinates (9104) and equivalent isotropic dis-
˚
P(1)–O(3) = 1.573 (2) A, P(1)–O(4) = 1.567 (2) A and P(1)–
˚
3
placement parameters (910 A ) for the title compound
2
˚
˚
C(1) = 1.820 (2) A, respectively. The bond angles are \O(2)–
P(1)–O(4) = 115.7 (1)°, \O(2)–P(1)–O(3) = 114.0 (2)°,
\O(4)–P(1)–O(3) = 103.3 (2)°, \O(2)–P(1)–C(1) = 115.1
(1)°, \O(3)–P(1)–C(1) = 106.5 (1)° and \O(2)–P(1)–
C(1) = 100.7 (6)°, respectively. Figure 1 represents an OR-
TEP [15, 16] diagram of the asymmetric unit of the molecule
x
y
z
U(eq)
41(1)
P(1)
9,900(1)
9,575(2)
7,653(1)
8,572(2)
5,964(2)
8,054(2)
8,368(2)
8,628(3)
9,005(3)
8,930(3)
9,905(3)
9,847(3)
8,796(4)
7,806(3)
7,871(3)
7,165(3)
7,464(3)
8,371(5)
6,130(5)
8,285(5)
7,472(4)
9,638(4)
1,325(1)
2,534(1)
1,502(1)
932(1)
O(1)
O(2)
O(3)
O(4)
O(5)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
67(1)
50(1)
55(1)
51(1)
82(1)
48(1)
46(1)
57(1)
62(1)
58(1)
64(1)
57(1)
60(1)
63(1 )
1,25(2)
1,27(2)
1,10(1)
92(1)
99(1)
10,137(2)
8,429(2)
10,690(2)
15,860(2)
10,376(2)
11,845(2)
12,722(2)
14,070(3)
14,554(2)
13,696(3)
12,360(2)
7,299(2)
819(1)
3,446(1)
2,080(1)
2,440(1)
2,226(1)
2,538(1)
3,085(1)
3,308(2)
2,987(1)
1,037(2)
267(1)
11,086(3)
6,330(3)
1,143(2)
412(2)
6,786(3)
12,330(3)
10,004(3)
16,788(3)
187(2)
-402(2)
3,240(2)
Fig. 1 ORTEP diagram of the molecule drawn at 50% probability
U(eq) is defined as one third of the trace of the orthogonalized Uij
tensor
˚
Table 3 Selected bond lengths (A) and bond angles (°) of the title
compound
˚
(A)
Bond lengths
Angles
(°)
P(1)–O(2)
P(1)–O(4)
P(1)–O(3)
P(1)–C(1)
O(1)–C(1)
O(5)–C(5)
O(5)–C(14)
O(3)–C(8)
O(4)–C(9)
C(3)–C(2)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
C(6)–C(7)
C(7)–C(2)
C(2)–C(1)
C(8)–C(11)
C(8)–C(10)
C(9)–C(13)
C(9)–C(12)
1.469(2)
1.567(2)
1.573(2)
1.820(2)
1.420(3)
1.378(3)
1.430(3)
1.464(3)
1.464(3)
1.379(3)
1.391(3)
1.374(4)
1.381(4)
1.381(3)
1.386(3)
1.521(3)
1.478(4)
1.492(4)
1.486(4)
1.524(4)
O(2)–P(1)–O(4)
O(2)–P(1)–O(3)
O(4)–P(1)–O(3)
O(2)–P(1)–C(1)
O(4)–P(1)–C(1)
O(3)–P(1)–C(1)
C(5)–O(5)–C(14)
C(8)–O(3)–P(1)
C(5)–C(4)–C(3)
C(4)–C(5)–O(5)
C(4)–C(5)–C(6)
O(5)–C(5)–C(6)
O(1)–C(1)–C(2)
O(1)–C(1)–P(1)
C(2)–C(1)–P(1)
O(3)–C(8)–C(11)
O(3)–C(8)–C(10)
C(11)–C(8)–C(10)
O(4)–C(9)–C(13)
O(4)–C(9)–C(12)
115.7(1)
114.0(2)
103.3(4)
115.1(1)
100.7(6)
106.5(1)
117.4(2)
123.6(1)
119.2(2)
125.3(3)
119.5(3)
115.2(3)
113.6(2)
104.9(1)
112.1(1)
108.8(2)
106.3(2)
113.5(3)
109.8(2)
104.9(2)
Fig. 2 The molecular packing for C14H23O5P viewed down the a axis
with atoms drawn as 30% probability ellipsoids. Dashed lines indicate
O–HꢀꢀꢀO intermolecular hydrogen bonds
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J Chem Crystallogr (2008) 38:761–764
References
Table 4 Hydrogen-bond geometry
D–HꢀꢀꢀA
d (D–H)
d (HꢀꢀꢀA)
˚
1.90 A
d (DꢀꢀꢀA)
\DHA
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˚
0.82 A
˚
O1–H1ꢀꢀꢀO2
2.715 (2) A 173.9°
with thermal ellipsoids at 50% probability values. Crystal
packing is stabilized by interatomic hydrogen bond interactions
between the doubly bonded phosphoryl O atom and the
hydroxyl H atom which link the molecules into chains along the
[011] plane of the unit cell (Fig. 2, Table 4) (symmetry code:
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Supplementary Material
CCDC-659487 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or
from the Cambridge Crystallographic Data Centre
(CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44(0)1223-336033; email: deposit@ccdc.cam.ac.uk.
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Acknowledgments The authors would like to acknowledge the key
Foundation of Science and Technology Project of China 2006
DFA43030 and National Natural Science Foundation of China (No.
20572061).
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