Struct Chem (2008) 19:765–770 DOI 10.1007/s11224-008-9361-4
ORIGINAL RESEARCH
Synthesis, characterization, crystal and molecular structure analysis of a novel 1-benzhydryl piperazine derivative: 1-benzhydryl-4-(2-nitro-benzenesulfonyl)-piperazine K. Vinaya Æ S. Naveen Æ C. S. Ananda Kumar Æ S. B. Benakaprasad Æ M. A. Sridhar Æ J. Shashidhara Prasad Æ K. S. Rangappa
Received: 9 November 2007 / Accepted: 16 July 2008 / Published online: 12 August 2008 Ó Springer Science+Business Media, LLC 2008
Abstract A novel 1-benzhydryl piperazine derivative 1-benzhydryl-4-(2-nitro-benzenesulfonyl)-piperazine was synthesized by the nucleophilic substitution of 1-benzhydryl piperazine with 2-nitro-benzenesulfonyl chloride. The product obtained was characterized spectroscopically and finally confirmed by X-ray diffraction study. The title compound, C23H23N3O4S crystallizes in the monoclinic space ˚, b = group C2/c with cell parameters a = 13.1120(9) A ˚ ˚ 21.4990(9) A, c = 16.655(1) A, b = 111.352(2)°, Z = 8, ˚ . The structure reveals that the piperand V = 4372.7(4) A azine ring is in a chair conformation. The geometry around the S atom is distorted tetrahedral. There is a large discrepancy in the bond angles around the piperazine N atoms. The structure is stablized by C–HO type intermolecular hydrogen bonding interactions. Keywords 1-Benzhydryl piperazine Nucleophilic substitution Crystal structure Distorted tetrahedron
Introduction The benzhydryl motif is a fundamental component present in drugs which are anti-histamines, anti-hypertensive, antimigraine, and anti-allergenic agents [1]. The piperazine
K. Vinaya C. S. Ananda Kumar S. B. Benakaprasad K. S. Rangappa (&) Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India e-mail:
[email protected];
[email protected] S. Naveen M. A. Sridhar J. Shashidhara Prasad Department of Studies in Physics, University of Mysore, Mysore 570006, India
nucleus is capable of binding to multiple receptors with high affinity and therefore it has been classified as a privileged structure [2]. Piperazines are found in various biologically active compounds across a number of different therapeutic areas [3] which include anti-fungal [4], anti-bacterial, antimalarial, anti-psychotic [5], and anti-depressant agents [6]. They are reported to possess good anti-tumor activity against colon, prostate, breast, lung, and leukemia tumors [7]. The piperazine ring and its derivatives are important cyclic components in the field of industry which are used as raw materials for hardening of the epoxy resins, corrosion inhibitors, insecticides, accelerators for rubber, urethane catalysts, and anti-oxidants. 1-Benzylpiperazine was originally synthesized as a potential anti-helminthic [8]. These derivatives of piperazine are found to possess excellent pharmacological activities such as vasodilator, hypotensive, anti-viral [9], and cerebral blood flow increasing actions [10]. They are found to have broad pharmacological action on central nervous system (CNS), especially on dopaminergic neurotransmission [11]. Sulfonamide drugs (widely known as ‘‘sulfa drugs’’) were the first anti-microbial drugs which paved the way for the antibiotic revolution in medicine. The first sulfonamide was trade named as Prontosil, which is a prodrug. Today, sulfonamides are among the most widely used anti-bacterial [12] agents in the world, chiefly because of their low cost, low toxicity, and excellent activity against common bacterial diseases. Sulfonamides can produce a variety of outward effects due partly to allergy, direct toxicity, allergic nephritis, and anemia [13]. Piperazine sulfonamides exhibit diverse pharmacological activities such as MMP-3 inhibition, anti-bacterial activity, and carbonic anhydrase inhibition [14]. In continuation of the search for such potent molecules, the title compound was synthesized by nucleophilic
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Struct Chem (2008) 19:765–770
Table 1 Crystal data and structure refinement Table
Table 2 Atomic coordinates and equivalent thermal parameters of the non-hydrogen atoms
Empirical formula
C23H23N3O4S
Formula weight
437.50
Atom
Crystal color, habit
White, rectangular
N1
0.4390(2)
0.4734(2)
0.1051(2)
0.0489(5)
Temperature
293(2)K ˚ 0.71073A
C2
0.4174(2)
0.4917(2)
0.2079(2)
0.0397(4)
Wavelength
C3
0.3717(2)
0.4212(2)
0.2517(2)
0.0366(4)
Crystal system
Monoclinic
C4
0.3468(2)
0.3189(2)
0.1952(2)
0.0375(4)
Space group
C2/c
0.3783(2)
0.3124(2)
0.0899(2)
0.0448(4)
Cell dimensions
˚ a = 13.1120(9) A ˚ b = 21.4990(9) A
N5 C6
0.4227(2)
0.3844(2)
0.0466(2)
0.0442(5)
˚ c = 16.655(1) A
O7 C8
0.4472(2) 0.4565(2)
0.3721(2) 0.5922(2)
-0.0421(2) 0.2609(2)
0.0617(5) 0.0538(6)
b = 111.352(2)° ˚3 4372.7(4) A
C9
0.2199(2)
0.2944(2)
0.1529(2)
0.0386(4)
Volume
C10
0.1861(2)
0.2244(2)
0.2156(2)
0.0472(5)
Z
8
C11
0.0703(2)
0.2056(2)
0.1807(3)
0.0571(6)
Density (calculated)
1.329Mg/m3
C12
-0.0141(2)
0.2561(2)
0.0826(3)
0.0559(6)
Absorption coefficient F000
0.183mm-1 1840
C13
0.0208(2)
0.3252(2)
0.0217(2)
0.0488(5)
C14
0.1353(2)
0.3456(2)
0.0545(2)
0.0439(5)
Crystal size
0.25 9 0.2 9 0.2mm3
N15
-0.0671(2)
0.3799(2)
-0.0843(3)
0.0685(6)
Theta range for data collection
2.31° to 25.03°
O16
-0.0353(2)
0.4392(2)
-0.1402(2)
0.0939(8)
Index ranges
-15 B h B 15
O17
-0.1682(2)
0.3650(2)
-0.1107(3)
0.1227(2)
-25 B k B 24
C18
0.3491(2)
0.4329(2)
0.3638(2)
0.0377(4)
-19 B l B 19
O19
0.3766(2)
0.3684(2)
0.4447(2)
0.0502(4)
Reflections collected
6771
N20
0.2939(2)
0.5154(2)
0.3696(2)
0.0452(4)
Independent reflections
3755 [Rint = 0.0198]
C21
0.2729(2)
0.5423(2)
0.4746(2)
0.0434(5)
Absorption correction
None
Refinement method
Full-matrix least-squares on F2
C22 C23
0.3371(2) 0.3204(2)
0.6179(2) 0.6435(2)
0.5527(2) 0.6559(3)
0.0534(6) 0.0614(7)
Data/restraints/parameters
3755 / 0 / 281
C24
0.2396(2)
0.5953(2)
0.6841(2)
0.0590(6)
Goodness-of-fit on F2
1.101
C25
0.1752(2)
0.5219(2)
0.6040(3)
0.0577(6)
Final R indices [I [ 2 r(I)]
R1 = 0.0433, wR2 = 0.1226
C26
0.1892(2)
0.4928(2)
0.4978(2)
0.0484(5)
R indices (all data)
R1 = 0.0514, wR2 = 0.1317
C27
0.1178(3)
0.4131(2)
0.4133(3)
0.0623(7)
Extinction coefficient
0.0044(5) ˚ -3 0.296 and -0.328 e.A
C28
0.2231(4) 0.6218(3) PP ¼ ð1=3Þ Uij ðai aj Þðai aj Þ
0.7994(3)
0.0948(2)
Largest diff. peak and hole
Ueq
x
y
i
substitution of 1-benzhydryl piperazine with 2-nitro-benzenesulfonyl chloride. The structure of the compound was established on the basis of Fourier transform infrared (FTIR) absorption spectroscopy, NMR, Mass spectroscopy, elemental analysis, and finally confirmed by X-ray crystallography.
z
Ueq
j
(triplet), m (multiplet). Mass spectra were recorded on a Trio 1000 Thermo Quest spectrometer. Elemental analyses (CHNS) were obtained on Vario EL III Elementar. Silica gel column chromatography was performed using Merck 7734 silica gel (60–120 mesh) and Merck made TLC plates.
Synthesis and characterization Experimental Synthesis of 1-benzhydryl piperazine (5) The melting points were determined using Veego model VMP-III melting point apparatus and are uncorrected. Infrared (IR) spectra were recorded using a Jasco FTIR-4100 series. Nuclear magnetic resonance (1H NMR) spectra were recorded on a Bruker AM-400 and chemical shifts (ppm, for d) relative to TMS as an internal standard. Spin multiplets are given as s (singlet), d (doublet), t
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A mixture of benzhydryl chloride 4 (1.0 eq), piperazine (1.0 eq) in N,N-dimethyl formamide, and anhydrous potassium carbonate (3.0 eq) was added and heated to 80 °C for 10 h. The reaction was monitored by TLC. Upon completion, the solvent was removed under reduced pressure and extracted with ethyl acetate. Finally, water wash
Struct Chem (2008) 19:765–770
767
˚) Table 3 Bond lengths (A
Table 4 Bond angles (°)
Atoms
Length
Atoms
Length
Atoms
Angle
Atoms
Angle
N1–C6
1.365(3)
C13–C14
1.381(3)
C6–N1–C2
124.1(2)
C14–C13–N15
117.9(2)
N1–C2
1.384(3)
C13–N15
1.473(3)
C3–C2–N1
120.1(2)
C13–C14–C9
119.2(2)
C2–C3
1.343(3)
N15–O17
1.218(3)
C3–C2–C8
128.0(2)
O17–N15–O16
123.0(3)
C2–C8
1.499(3)
N15–O16
1.223(3)
N1–C2–C8
111.9(2)
O17–N15–C13
118.3(3)
C3–C18
1.487(3)
C18–O19
1.232(2)
C2–C3–C18
124.0(2)
O16-N15–C13
118.7(2)
C3–C4
1.518(3)
C18–N20
1.348(3)
C2–C3–C4
122.1(2)
O19–C18–N20
122.4(2)
C4–N5
1.472(2)
N20–C21
1.431(3)
C18–C3–C4
113.9(2)
O19–C18–C3
121.1(2)
C4–C9
1.525(3)
C21–C22
1.391(3)
N5–C4–C3
110.2(2)
N20–C18–C3
116.6(2)
N5–C6
1.346(3)
C21–C26
1.398(3)
N5–C4–C9
111.2(2)
C18–N20–C21
124.2(2)
C6–O7
1.232(3)
C22–C23
1.376(4)
C3–C4–C9
109.7(2)
C22–C21–C26
120.8(2)
C9–C14 C9–C10
1.388(3) 1.390(3)
C23–C24 C24–C25
1.390(4) 1.379(4)
C6–N5–C4 O7–C6–N5
126.9(2) 122.4(4)
C22–C21–N20 C26–C21–N20
119.0(2) 120.2(2)
C10–C11
1.389(3)
C24–C28
1.515(4)
O7–C6–N1
120.9(2)
C23–C22–C21
120.1(2)
C11–C12
1.380(4)
C25–C26
1.403(3)
N5–C6–N1
116.8(2)
C22–C23–C24
121.1(2)
C12–C13
1.375(3)
C26–C27
1.491(3)
C14–C9–C10
118.6(2)
C25–C24–C23
117.8(2)
C14–C9–C4
120.3(2)
C25–C24–C28
120.9(3)
C10–C9–C4
121.1(2)
C23–C24–C28
121.2(3)
C11-C10–C9
121.0(2)
C24–C25–C26
123.2(2)
C12–C11–C10
120.6(2)
C21–C26–C25
116.9(2)
C13–C12–C11
117.8(2)
C21–C26–C27
121.5(2)
C12–C13–C14
122.9(2)
C25–C26–C27
121.6(2)
C12–C13–N15
119.2(2)
was given to organic layer and dried with anhydrous sodium sulfate. The solvent was evaporated to get the crude product, which was purified by column chromatography over silica gel (60–120 mesh) using hexane/ethyl acetate (6:4) as an eluent. The product obtained 5 was a white crystalline solid. Synthesis of 1-benzhydryl-4-(2-nitro-benzenesulfonyl)piperazine (6) A solution of 1-benzhydryl piperazine 5 (0.5 g, 1.98 mmol) in dry dichloromethane was taken and cooled to 5 °C in an ice bath. Then triethylamine (0.601 g, 5.94 mmol) was added to the cold reaction mixture and stirred for 10 min. Then 2-nitro-benzenesulfonyl chloride (0.438 g, 1.98 mmol) was added to the reaction mixture and the reaction mixture was stirred at room temperature for 5 h. The reaction was monitored by TLC. On completion of the reaction, the solvent was removed under reduced pressure and the residue was taken in water and extracted with ethyl acetate. Finally water wash was given to the organic layer and dried with anhydrous sodium sulfate. The solvent was evaporated to get a crude product which was purified by column chromatography over silica gel using hexane/ethyl acetate (8:2) as an eluent. The pure product obtained was a white crystalline solid (0.77 g, 90%). The product obtained was dissolved in ethyl acetate. White crystals developed after 4 days due to the slow evaporation of the solvent. M. P: 160–162 °C. IR (KBr, cm-1): 1350, 1280, 1530, 1380. 1 H NMR (400 MHz, DMSO): d 7.38 (d, 4H, Ar–H), 7.27 (t, 4H, Ar–H), 7.95–8.0 (m, 3H, Ar–H), 7.80 (t, 1H, Ar–H), 7.15 (t, 2H, Ar–H), 4.35 (s, 1H, –CH), 3.3 (t, 4H, –CH2–),
2.35 (t, 4H, –CH2–) MS (ESI + ion): m/z = 436.5. Anal. Calcd. for C23H33N3O4S (in %): C—63.14, H—5.30, N— 9.6, S—7.33. Found C—63.10, H—5.25, N—9.3, S—7.29.
Results and discussion Spectroscopic analysis The presence of N–H proton at 2.2 d value in 1-benzhydryl piperazine 5 and the absence of this proton peak in proton NMR spectra confirms the formation of product 6. The signal due to phenyl protons adjacent to the carbon atom bearing the nitro group are highly de-shielded and showed multiplets at d = 7.95–8.00 ppm. The FTIR spectrum showed the asymmetric stretching of S=O at 1350 cm-1 symmetric stretching at 1280 cm-1. The presence of nitro group can be identified from the two intense absorption bands at 1530 cm-1 and 1380 cm-1 for the asymmetric stretching and symmetric vibrations, respectively. Crystal structure determination A single crystal of the title compound with dimensions 0.25 9 0.2 9 0.2 mm3 was chosen for an X-ray diffraction
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Struct Chem (2008) 19:765–770
O MgBr SOCl2 ,CH2Cl2
dry THF +
OH
r.t., 2 hours
2 hours
2
1
3
HN
NH 10 hours
Cl
N
NH
K2CO3 ,DMF
4
5 O S
TEA, MDC, 5 hours
Cl
O NO2 O N
N
S O
6
Fig. 1 Reaction scheme
study. The data were collected on a DIPLabo Image Plate system equipped with a normal focus, 3 kW sealed X-ray source [graphite monochromated MoKa]. The crystal-todetector distance is fixed at 120 mm with a detector area of 441 9 240 mm2. Thirty six frames of data were collected at room temperature by the oscillation method. Each exposure of the image plate was set to a period of 400 s. Successive frames were scanned in steps of 5° per minute with an oscillation range of 5°. Image processing and data reduction were done using Denzo [15]. The reflections were merged with Scalepack [16]. All the frames could be indexed using a centered monoclinic lattice. The structure was solved by direct methods using SHELXS-97 [17]. All the non-hydrogen atoms were revealed in the first Fourier map itself. Full-matrix least squares refinement using
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SHELXL-97 [18] with isotropic temperature factors for all the atoms converged the residuals to R1 = 0.1326. Refinement of non-hydrogen atoms with anisotropic parameters was started at this stage. The hydrogen atoms were placed at chemically acceptable positions and were allowed to ride on the parent atoms. Two hundred and eightyone parameters were refined with 3755 unique reflections which converged the residuals to R1 = 0.0433. The details of the crystal data and refinement are given in Table 1.1 The final atomic coordinates and equivalent thermal parameters 1
‘‘CCCDC 650929 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033. email:
[email protected]’’.
Struct Chem (2008) 19:765–770
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Fig. 2 ORTEP of the molecule with thermal ellipsoids drawn at 30% probability ˚ °) Table 5 Hydrogen-bonding geometry (A D–HA
D–H H–A D–A
D–HA Symmetry Codes
C2–H2AO9
0.97
2.45
2.857(3) 105
C13–H13O9 0.93
2.53
3.360(3) 149
x, -y, 1/2 + z
Note: D–H and H–A distances are essentially standard values and are not derived from the experiment
of the non-hydrogen atoms are listed in Table 2. Tables 3 and 4 give the list of bond distances and bond angles of nonhydrogen atoms, respectively. The bond lengths and bond angles are in good agreement with the standard values. Figures 1, 2 and 3 represent the ORTEP [19] of the molecule with thermal ellipsoids drawn at 30% probability. A study of the torsion angles, asymmetric parameters, and least-square plane calculations reveals that the piperazine ring in the structure is in a chair conformation.2 This is con˚, firmed by the puckering parameters [20] Q = 0.5885(23) A 2
Many molecules have as a part or in full, the closed rings. In these cases the planarity of the ring is an important conformational feature. If the ring is not planar, i.e. the sum of the absolute values of the torsion angle is not equal to zero, it is possible to describe the conformation of the ring in terms of well known shapes such as boat, crown, chair, etc. In the case of a chair conformation, the torsion angles will be alternating between 60 °C and -60 °C (In actual, the modulus of the torsion angle can be in the range of 50 °C–70 °C ). To understand the non-planarity of the ring, Cremer and Pople proposed a general definition of ring-puckering coordinates which can be applied without approximation to any cyclic molecule given only the coordinates of the nuclear positions of the atoms in the ring. This analysis can be applied to any of the rings of any size and it gives us a
Fig. 3 Packing of the molecules when viewed along the c axis. The dashed lines represent the hydrogen bonds
h = 6.35(23)° and / = 154(2)°. The ring puckering analysis revealed that the piperazine ring has a weighted average ˚ and a weighted ring bond distance of 1.4810(13, 88) A average torsion angle of 59.31(9,144)°. The conformation of the attachment of the diphenylmethyl and the sulfonyl groups to the piperazine ring are well described by the torsion
Footnote 2 continued more systematic description of the possible geometrical structures for larger rings containing seven or more atoms.
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angle values of 175.73(18)° and -168.72(17)° for C19–N4– C3–C2 and S7–N1–C6–C5, respectively, i.e., they adopt + antiperiplanar and -antiperiplanar conformations with respect to one another. The bonds N1–S7 and N4–C19 connecting the sulfonyl and the diphenylmethyl groups make an angle of 84.51(11)° and 75.57(14)°, respectively, with the Cremer and Pople plane [20] of the piperazine ring and thus are in the equatorial plane of the piperazine ring. The dihedral angle between the least-square plane of the piperazine ring and the nitrophenyl ring bridged by the sulfonyl group is 80.37(14)°. The two phenyl rings bridged by the central carbon atom are planar within the experimental limits and they make a dihedral angle of 68.93(18)° with each other. The piperazine ring makes an angle of 77.02(16)° and 71.92(16)° with the least-square planes of the phenyl rings C20C25 and C26C31, respectively. These values are lesser than the corresponding values reported for 1-benzhydryl piperazine [21] and 1-[(4-chloro-phenyl)-phenylmethyl]piperazine [22]. The angular disposition of the bonds about the S atom shows significant deviation from that of a regular tetrahedron with the largest deviations being observed for the O–S–O [O8–S7–O9 = 119.74(9)°] and O–S–N [O9–S7– N1 = 107.84(8)°] angles. This widening of the angles is due to the repulsive interactions between the S=O bonds and the non-bonded interactions involving the two S–O bonds and the varied steric hindrance of the substituents. The structure thus has less steric interference. The S–N ˚ ) lies within the expected range bond distance (1.635(2) A ˚ . The reduction of the N1–S7–C10 angle to of 1.63-1.69A 106.78(9)° from the ideal tetrahedral value is attributed to the Thorpe-Ingold effect [23]. The nitro group is twisted out of the plane of the adjacent aryl ring as indicated by the torsion angle values of -74.9(2)° and -78.3(2)° for C12– C11–N16–O17 and C10–C11–N16–O18, respectively. This twisted conformation may be due to the occurrence of the C–HO hydrogen bonds involving the nitro group in the structure. The bond angle C6–N1–C2 = 112.1(2)° is significantly larger than C3-N4-C5 = 107.8(2)°. This difference in angle seems to result from the steric hindrance caused by the sulfonic group attached to the piperazine N atom. The sulfonyl atoms O8 and O9 are oriented in +synclinal and -synperiplanar conformations, respectively, as indicated by the torsion angle values of 56.6(2)° and -37.5(2)° for C6–N1–S7–O8 and C2–N1– S7–O9, respectively. The structure exhibits intermolecular hydrogen bonds of the type C–HO. The observed hydrogen bonds are tabulated in Table 5. The packing of
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Struct Chem (2008) 19:765–770
the molecules when viewed down the a axis indicate that the molecules are interlinked by this hydrogen bond to form a chain like structure (Fig. 3). Acknowledgments The authors are grateful to Department of Science and Technology and Government of India for financial assistance under the projects SP/I2/FOO/93 and UGC-SAP(PhaseI)No.F.540/10/DRS/2004(SAP-I).
References 1. Rafael F, Jose AO, Santiago G, Manuel MR, Aurelio S. (1989) Ferrer International. S. A., US-4883797 2. Dinsmore CJ, Beshore DC (1953) Tetrahedron 58:3297 3. Martin Berkheij, Lisan van der Sluis, Claudia Sewing, Dennis J. den Boer, Jan Willem Terpstra, Henk Hiemstra, Wouter I. Iwema Bakker, Adri van den Hoogenband Jan H. van Maarseveen (1929) Tetrahedron Lett 15:2369 4. Upadhayaya RS, Sinha N, Jain S, Kishore N, Chandra R, Arora SK (2004) Bioorg Med Chem 12:2225 5. Choudhary P, Kumar R, Verma K (2006) J Org Chem 14: 1819 6. Korosi J, Gabriella SNC, Konya LN, Lujza ENP, Bolya BNK, Eniko K (1974) EGYT., US-3865828 7. Hulme C, Cherrier MP (1999) Tetrahedron Lett 40: 5295 8. Campbell H, Cline W, Evans M, Lloyd J, Peck AW (1973) Eur J Clin Pharma 6:170 9. Chern J-H, Shia K-S, Hsu T-A, Tai C-L, Lee C-C, Lee Y-C, Chang C-S, Tseng S-N, Shih S-R (2004) Bioorg Med Chem 14:2519. 10. Yoshikazu O, Katsumi I (1980) Hirata Minor US Patent 4:582 11. Kimara M, Masuda T, Yamada K (2003) Bioorg Med Chem 11:3953 12. Bertram GK (1995) Basic and Clinical Pharmacology. 6th ed, University of California, San Francisco 13. Gordin FM, Simon GL, Wofsy CB, Mills J (1984) Ann Intern Med 100:495 14. Ambrose AE, William W (2003) J Med Chem 44:3849 15. Otwinowski Z, Minor W (1997) Methods in Enzymology: Macromolecular Crystallography. In: Jr Carter CW , Sweet RM (eds) vol 276, Academic Press, NY p 307 16. Mackay S, Gillmore CJ, Edwards C, Shankland K (1999) maXus, Computer program for the solution and refinement of crystal structures; Bruker Nonius. The Netherlands, MacScience, Japan and The University of Glasgow 17. Sheldrick GM (1997) SHELXS-97 Program for Crystal Structure Solution. University of Go¨ttingen, Germany 18. Sheldrick GM (1997) SHELXS-97 Program for Crystal Structure Solution. University of Go¨ttingen, Germany 19. Spek AL (1998) Acta Cryst A46:C34 20. Cremer D, Pople JA (1975) J Am Chem Soc B12:1354 21. Naveen S, Nanjunda Swamy S, Basappa Prabhuswamy B, Sridhar MA, Shashidhara Prasad J, Rangappa KS (2006) J Anal Sci 22:x43 22. Hu XR, Gu JM, Lu GL (2003) Z Kristallogr NCS 218:497 23. Bassindale A (1984) The third dimension in organic chemistry. Wiley, New York
