organic papers
Acta Cryst.(2004). E60, o1851±o1853 DOI: 10.1107/S1600536804022366 Jem-Mau Loet al. C10H11BO3
o1851
Acta Crystallographica Section EStructure Reports Online
ISSN 1600-5368
3-(4-Dihydroxyborylphenyl)cyclobutanone
Jem-Mau Lo,aShyh-Ming Chen,b
Mei-Hsun Chen,aYu-Jen Chen,a
Fen-Ling Liaocand
Tian-Huey Lud*
aDepartment of Nuclear Science, National Tsing
Hua University, Hsinchu 300, Taiwan,
bComputer and Communication Center,
National Tsing Hua University, Hsinchu 300, Taiwan,cDepartment of Chemistry, National
Tsing Hua University, Hsinchu 300, Taiwan, anddDepartment of Physics, National Tsing Hua
University, Hsinchu 300, Taiwan
Correspondence e-mail: [email protected]
Key indicators
Single-crystal X-ray study T= 294 K
Mean(C±C) = 0.002 AÊ Rfactor = 0.034 wRfactor = 0.102
Data-to-parameter ratio = 11.2
For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.
#2004 International Union of Crystallography Printed in Great Britain ± all rights reserved
The title compound, C10H11BO3, may be developed as a potent boron neutron capture therapy (BNCT) drug for hepatoma treatment. The compound was obtained as transparent rectangular plate crystals. Intermolecular hydrogen bonds and±interactions help stabilize the crystal structure.
Comment
Hepatoma is one of the most prevalent malignant tumors occurring in Taiwan. Because the symptoms of hepatoma are not obvious and most patients would incur cirrhosis at the same time, it is dif®cult to treat hepatoma by surgical resec-tion. Hepatoma treatment is also not very effective by means of chemical therapy or radiation therapy; boron neutron capture therapy (BNCT) has been recently considered as an alternative useful method for treating hepatoma (Ariset al., 2004). The title compound, (I), has recently been developed in our laboratory as a potent BNCT agent for hepatoma treat-ment (Lo et al., 2003). The compound has been successfully synthesized and grown as crystals. The crystal structure is reported here.
There exist two strong [O1ÐH1O O2(2ÿx,ÿy,ÿz) and O2ÐH2O O1(2ÿx,1
2+y,12ÿz)] hydrogen bonds and one weak [C10ÐH10B O3(x, ÿ1
2ÿy, zÿ12)] hydrogen bond, with bond lengths (and angles) of 2.834 (3) AÊ [166 (2)],
3.039 (4) AÊ [160 (3)] and 3.447 (4) AÊ [166 (3)], respectively.
In addition to the intermolecular hydrogen bonds, the crystal packing involves intermolecular ± interactions, mainly between cyclobutanone rings, (1ÿx,ÿy,ÿz), with a distance of 4.267 (4) AÊ, between benzene rings, (ÿx,ÿy, 1ÿz), with a distance of 4.770 (4) AÊ, and between the benzene ring and the cyclobutanone ring at (1ÿx, ÿy, 1ÿz), with a distance of 4.874 (4) AÊ. The benzene ring has a maximum deviation of
Received 18 August 2004 Accepted 9 September 2004 Online 25 September 2004
0.0047 (10) AÊ from its least-squares plane. The maximum deviation from the mean plane of the four-membered cyclo-butanone ring is 0.0423 (9) AÊ. The benzene ring is almost perpendicular [86.71 (7)] to the cyclobutanone ring and is
coplanar [7.43 (9)] with the plane formed by atoms C1, O1
and O2.
The BÐC1 distance of 1.558 (2) AÊ is in good agreement with comparable phenylboronic acids where values range from 1.526 AÊ in p-bromophenylboronic acid (Zvonkova &
Gluskova, 1958) to 1.597 AÊ in
6-bis(tri-¯uoromethyl)phenyldihydroxyborane (Cornet et al., 2003). BÐO1 [1.364 (2) AÊ] and BÐO2 [1.371 (2) AÊ] lie at the upper end of the corresponding range, viz. 1.323 AÊ in (O,O0
)-[hydroxy[4-(dihydroxyboryl)phenyl]boron] bis(dimethyl-glyoximato)aquamethylcobalt trihydrate (Dreos et al., 2003) to 1.376 AÊ inl-p-boronophenylalanine (Shullet al., 2000). The situation is different in cyclo-tris[bis(penta¯uoro-phenyl)borinic acid] (Beringhelli et al., 2003), where steric crowding by the six penta¯uorophenyl ligands results in much longer BÐO distances, ranging from 1.519 to 1.535 AÊ.
Experimental
The precursor for synthesizing the title compound, 3-(4-borono-phenyl)cyclobutanone ethylene ketal, was obtained by a previously reported process (Fu, 2002; Srivastavaet al., 1999). A 100 ml round-bottomed ¯ask was charged with 3-(4-dihydroxyborylphenyl)cyclo-butanone ethylene ketal (5.8 mmol, 1.36 g) in methanol (14 ml), along with concentrated hydrochloric acid (10 drops). The contents of the ¯ask were stirred overnight at room temperature, and then the solvent was removed under reduced pressure by a rotary evaporator. The residue was dissolved in diethyl ether and washed with water and
then brine. The organic layer was collected and dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product was puri®ed using silica gel chromatography (202 cm, 20 and 40% ethyl acetate in hexane) to obtain the ®nal product as a white solid (0.46 g, 33.8% yield): Rf= 0.46 (50% ethyl acetate in hexane, silica gel TLC). For recrystallization, the white solid was dissolved in diethyl ether to form a near saturated solution, which was ®ltered through a ®lter paper. The resulting clear ®ltrate was poured into a glass column bottle, covered with a ®lter paper and kept in a refrigerator at 268 K for 24 h, allowing the solvent to evaporate gradually. With the remaining 3 ml of solution, the bottle was moved from the refrigerator and kept at room temperature to expedite the evaporation. Rectangular crystals formed after some time and suitable crystals were harvested for X-ray structure analysis. M.p. 367±371 K.1H NMR (CDCl
3):7.71 (d,J= 7.3 Hz, 2H), 7.32 (d,J=
7.3 Hz, 2H), 3.64 (m, 1H), 3.47 (m, 2H), 3.22 (m, 2H).13C NMR
(CDCl3):206.38, 148.13, 135.64, 126.24, 54.43, 28.56.
Crystal data
C10H11BO3 Mr= 190.00 Monoclinic,P21=c a= 11.4645 (11) AÊ b= 9.8317 (9) AÊ c= 8.3674 (8) AÊ = 98.551 (2) V= 932.65 (15) AÊ3 Z= 4
Dx= 1.353 Mg mÿ3 MoKradiation Cell parameters from 5680
re¯ections = 2.0±28.0 = 0.10 mmÿ1 T= 294 (2) K
Rectangular plate, colourless 0.150.100.05 mm
Data collection
Bruker SMART CCD area-detector diffractometer
'and!scans
Absorption correction: multi-scan (SHELXTL; Bruker, 2000) Tmin= 0.927,Tmax= 0.993 5481 measured re¯ections
1915 independent re¯ections 1198 re¯ections withI> 2(I) Rint= 0.076
max= 26.4 h=ÿ14!12 k=ÿ11!12 l=ÿ10!10
Re®nement
Re®nement onF2 R[F2> 2(F2)] = 0.034 wR(F2) = 0.102 S= 0.96 1915 re¯ections 171 parameters
All H-atom parameters re®ned w= 1/[2(Fo2)(0.1P)2]
whereP= (Fo2+ 2Fc2)/3 (/)max< 0.001
max= 0.15 e AÊÿ3 min=ÿ0.13 e AÊÿ3
organic papers
o1852
Jem-Mau Loet al. C10H11BO3 Acta Cryst.(2004). E60, o1851±o1853Figure 1
The molecular structure of the title compound, showing 30% probability displacement ellipsoids.
Figure 2
Table 1
Selected geometric parameters (AÊ,).
O1ÐB 1.364 (2)
O2ÐB 1.371 (2) O3ÐC9C1ÐB 1.200 (2)1.558 (2)
C2ÐC1ÐB 122.9 (1)
C6ÐC1ÐB 120.8 (1)
O3ÐC9ÐC10 134.0 (2)
O3ÐC9ÐC8 132.8 (2)
O1ÐBÐO2 117.1 (1)
O1ÐBÐC1 119.1 (1)
O2ÐBÐC1 123.8 (1)
H atoms were located in a difference Fourier synthesis and re®ned isotropically [CÐH = 0.924 (17)±1.009 (19) AÊ].
Data collection:SMART(Bruker, 1998); cell re®nement:SAINT
(Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997); molecular graphics:
ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication:SHELXL97.
The authors thank the National Science Council, Republic of China, for support under grant Nos. NSC 92-2745-P-075-001, and the Veterans General Hospitals University System of
Taiwan Joint Research Program, Tsou's Foundation, for support under grant No. VGHUST 93-G2-02.
References
Aris, Z., Tazio, P., Ubaldo, P., Francesca, F., Saverio, A. & Laura, R. (2004). BNCT Pavia Project, University of Pavia, Italy.
Beringhelli, T., D'Alfonso, G., Donghi, D., Maggioni, D., Mercandelli, P. & Sironi, A. (2003).Organometallics,22, 1588±1590.
Bruker (1998).SMART. Version 5.054. Bruker AXS Inc., Madison, Wisconsin, USA.
Bruker (2000).SHELXTL(Version 6.1) andSAINT(Version 6.02a). Bruker AXS Inc., Madison, Wisconsin, USA.
Cornet, S. M., Dillon, K. B., Entwistle, C. D., Fox, M. A., Goeta, A. E., Goodwin, H. P., Marder, T. B. & Thompson, A. L. (2003).Dalton Trans. pp. 4395±4405.
Dreos, R., Nardin, G., Randaccio, L., Siega, P. & Tauzher, G. (2003).Inorg. Chem.42, 612±614.
Farrugia, L. J. (1997).J. Appl. Cryst.30, 565.
Fu, I. Y. (2002). MS thesis, National Tsing Hua University, Taiwan. Lo, J. M., Wu, P. Y., Fu, I. Y. & Cheng, H. W. (2003).J. Nucl. Med.44, 309. Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of
GoÈttingen, Germany.
Shull, B. K., Spielvogel, D. E., Gopalaswamy, R., Sankar, S., Boyle, P. D., Head, G. & Devito, K. (2000).J. Chem. Soc. Perkin Trans.2, 557±559.
Srivastava, R. R., Singhaus, R. R. & Kaballa, G. W. (1999).J. Org. Chem.64, 8495±8500.
Zvonkova, Z. V. & Gluskova, V. P. (1958). Kristallogra®ya (in Russian) (Crystallogr. Rep.),3, 559±562.
organic papers
supporting information
sup-1 Acta Cryst. (2004). E60, o1851–o1853
supporting information
Acta Cryst. (2004). E60, o1851–o1853 [https://doi.org/10.1107/S1600536804022366]
3-(4-Dihydroxyborylphenyl)cyclobutanone
Jem-Mau Lo, Shyh-Ming Chen, Mei-Hsun Chen, Yu-Jen Chen, Fen-Ling Liao and Tian-Huey Lu
3-(4-dihydroxyborylphenyl)cyclobutanone
Crystal data
C10H11BO3
Mr = 190.00 Monoclinic, P21/c
a = 11.4645 (11) Å
b = 9.8317 (9) Å
c = 8.3674 (8) Å
β = 98.551 (2)°
V = 932.65 (15) Å3
Z = 4
F(000) = 400
Dx = 1.353 Mg m−3
Mo Kα radiation, λ = 0.71073 Å Cell parameters from 5680 reflections
θ = 2.0–28.0°
µ = 0.10 mm−1
T = 294 K
Rectangular plate, colourless 0.15 × 0.10 × 0.05 mm
Data collection
Bruker SMART CCD area-detector diffractometer
Radiation source: fine-focus sealed tube Graphite monochromator
φ and ω scans
Absorption correction: psi scan (SHELXTL; Bruker, 2000)
Tmin = 0.927, Tmax = 0.993
5481 measured reflections 1915 independent reflections 1198 reflections with I > 2σ(I)
Rint = 0.076
θmax = 26.4°, θmin = 1.8°
h = −14→12
k = −11→12
l = −10→10
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.034
wR(F2) = 0.102
S = 0.96 1915 reflections 171 parameters 0 restraints
Primary atom site location: structure-invariant direct methods
Secondary atom site location: difference Fourier map
Hydrogen site location: inferred from neighbouring sites
All H-atom parameters refined
w = 1/[σ2(F
o2)(0.1P)2]
where P = (Fo2 + 2Fc2)/3
(Δ/σ)max < 0.001
Δρmax = 0.15 e Å−3
Δρmin = −0.13 e Å−3
Special details
supporting information
sup-2 Acta Cryst. (2004). E60, o1851–o1853
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2,
conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used
only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2
are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x y z Uiso*/Ueq
O1 0.96582 (10) −0.12063 (10) 0.17237 (13) 0.0421 (3)
O2 0.97563 (10) 0.11504 (11) 0.14493 (13) 0.0439 (3)
O3 0.51464 (13) −0.17211 (14) 0.97457 (18) 0.0791 (5)
C1 0.86396 (11) 0.01649 (13) 0.36538 (15) 0.0306 (3)
C2 0.81769 (12) 0.13894 (14) 0.41091 (17) 0.0341 (3)
C3 0.74740 (12) 0.14610 (15) 0.53204 (16) 0.0332 (3)
C4 0.72100 (11) 0.03049 (13) 0.61429 (17) 0.0316 (3)
C5 0.76642 (13) −0.09298 (15) 0.56952 (18) 0.0402 (4)
C6 0.83532 (13) −0.09938 (15) 0.44819 (18) 0.0389 (4)
C7 0.64392 (12) 0.03936 (15) 0.74417 (17) 0.0352 (3)
C8 0.68371 (15) −0.03663 (19) 0.9057 (2) 0.0457 (4)
C9 0.56397 (14) −0.10426 (15) 0.88585 (19) 0.0471 (4)
C10 0.52803 (15) −0.0457 (2) 0.7210 (2) 0.0506 (5)
B 0.93881 (14) 0.00511 (15) 0.22510 (19) 0.0316 (4)
H1O 0.997 (2) −0.122 (2) 0.082 (3) 0.082 (7)*
H2O 0.9727 (15) 0.185 (2) 0.188 (2) 0.055 (6)*
H2 0.8279 (14) 0.2214 (17) 0.3561 (19) 0.048 (4)*
H3 0.7165 (13) 0.2321 (17) 0.5588 (18) 0.046 (4)*
H5 0.7478 (14) −0.1745 (16) 0.626 (2) 0.050 (5)*
H6 0.8603 (14) −0.1840 (17) 0.4195 (19) 0.048 (4)*
H7 0.6289 (14) 0.1335 (16) 0.758 (2) 0.055 (5)*
H8A 0.6992 (16) 0.0169 (18) 1.004 (3) 0.069 (6)*
H8B 0.7483 (17) −0.1051 (19) 0.898 (2) 0.070 (5)*
H10B 0.5274 (19) −0.112 (2) 0.638 (2) 0.081 (6)*
H10A 0.4530 (19) 0.0064 (19) 0.710 (3) 0.084 (7)*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
O1 0.0560 (7) 0.0335 (6) 0.0429 (6) 0.0020 (4) 0.0271 (5) −0.0007 (4)
O2 0.0607 (7) 0.0324 (6) 0.0457 (6) −0.0024 (5) 0.0308 (5) −0.0011 (5)
O3 0.0899 (10) 0.0615 (9) 0.0981 (11) −0.0106 (7) 0.0546 (9) 0.0183 (7)
C1 0.0291 (7) 0.0328 (7) 0.0306 (7) −0.0003 (5) 0.0071 (6) −0.0006 (5)
C2 0.0378 (8) 0.0309 (8) 0.0353 (8) −0.0017 (6) 0.0106 (6) 0.0026 (6)
C3 0.0339 (8) 0.0305 (8) 0.0370 (8) 0.0015 (5) 0.0107 (6) −0.0015 (6)
C4 0.0290 (7) 0.0353 (8) 0.0317 (7) −0.0021 (5) 0.0080 (6) 0.0000 (6)
C5 0.0470 (9) 0.0308 (8) 0.0473 (9) 0.0014 (6) 0.0215 (7) 0.0062 (6)
C6 0.0439 (9) 0.0297 (8) 0.0476 (9) 0.0045 (6) 0.0219 (7) 0.0022 (6)
C7 0.0354 (8) 0.0362 (8) 0.0364 (8) −0.0017 (6) 0.0131 (6) −0.0008 (6)
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sup-3 Acta Cryst. (2004). E60, o1851–o1853
C9 0.0554 (10) 0.0370 (9) 0.0559 (10) −0.0021 (7) 0.0310 (8) −0.0023 (7)
C10 0.0369 (9) 0.0737 (12) 0.0450 (10) −0.0100 (8) 0.0182 (8) −0.0060 (9)
B 0.0324 (8) 0.0304 (8) 0.0330 (8) −0.0006 (6) 0.0082 (7) 0.0025 (6)
Geometric parameters (Å, º)
O1—B 1.364 (2) C4—C7 1.5017 (19)
O1—H1O 0.88 (2) C5—C6 1.377 (2)
O2—B 1.371 (2) C5—H5 0.971 (17)
O2—H2O 0.78 (2) C6—H6 0.924 (17)
O3—C9 1.200 (2) C7—C8 1.553 (2)
C1—C2 1.3914 (19) C7—C10 1.557 (2)
C1—C6 1.3976 (19) C7—H7 0.952 (16)
C1—B 1.558 (2) C8—C9 1.512 (2)
C2—C3 1.3873 (19) C8—H8A 0.97 (2)
C2—H2 0.948 (16) C8—H8B 1.009 (19)
C3—C4 1.3854 (19) C9—C10 1.495 (2)
C3—H3 0.957 (16) C10—H10B 0.95 (2)
C4—C5 1.3939 (19) C10—H10A 0.99 (2)
B—O1—H1O 115.3 (14) C8—C7—C10 89.13 (12)
B—O2—H2O 115.7 (13) C4—C7—H7 106.5 (11)
C2—C1—C6 116.25 (13) C8—C7—H7 113.2 (10)
C2—C1—B 122.9 (1) C10—C7—H7 111.8 (10)
C6—C1—B 120.8 (1) C9—C8—C7 88.36 (12)
C3—C2—C1 122.04 (13) C9—C8—H8A 112.4 (11)
C3—C2—H2 115.9 (10) C7—C8—H8A 118.0 (11)
C1—C2—H2 121.9 (10) C9—C8—H8B 111.2 (10)
C4—C3—C2 120.99 (13) C7—C8—H8B 112.9 (11)
C4—C3—H3 119.6 (9) H8A—C8—H8B 111.8 (16)
C2—C3—H3 119.5 (9) O3—C9—C10 134.0 (2)
C3—C4—C5 117.59 (13) O3—C9—C8 132.8 (2)
C3—C4—C7 120.49 (12) C10—C9—C8 93.05 (12)
C5—C4—C7 121.91 (13) C9—C10—C7 88.80 (12)
C6—C5—C4 121.06 (13) C9—C10—H10B 112.2 (12)
C6—C5—H5 121.0 (10) C7—C10—H10B 111.9 (13)
C4—C5—H5 118.0 (10) C9—C10—H10A 113.7 (13)
C5—C6—C1 122.07 (14) C7—C10—H10A 116.5 (12)
C5—C6—H6 117.8 (10) H10B—C10—H10A 111.9 (18)
C1—C6—H6 120.1 (10) O1—B—O2 117.1 (1)
C4—C7—C8 118.28 (12) O1—B—C1 119.1 (1)
C4—C7—C10 117.50 (13) O2—B—C1 123.8 (1)
C6—C1—C2—C3 0.2 (2) C5—C4—C7—C10 −57.99 (19)
B—C1—C2—C3 177.44 (12) C4—C7—C8—C9 −127.08 (13)
C1—C2—C3—C4 0.5 (2) C10—C7—C8—C9 −6.00 (13)
C2—C3—C4—C5 −0.7 (2) C7—C8—C9—O3 −169.58 (19)
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sup-4 Acta Cryst. (2004). E60, o1851–o1853
C3—C4—C5—C6 0.2 (2) O3—C9—C10—C7 169.5 (2)
C7—C4—C5—C6 178.88 (14) C8—C9—C10—C7 −6.23 (13)
C4—C5—C6—C1 0.6 (2) C4—C7—C10—C9 127.83 (14)
C2—C1—C6—C5 −0.8 (2) C8—C7—C10—C9 6.06 (13)
B—C1—C6—C5 −178.07 (13) C2—C1—B—O1 −170.26 (13)
C3—C4—C7—C8 −134.23 (15) C6—C1—B—O1 6.8 (2)
C5—C4—C7—C8 47.12 (19) C2—C1—B—O2 6.7 (2)
