Synthesis and crystal structure of 1-benzhydryl-4-methane-sulfonyl- piperazine

Article abstract of DOI:10.1080/15421400701693542

The title compound, 1-benzhydryl-4-methanesulfonyl-piperazine, was synthesized by the nucleophilic substitution of 1-benzhydryl-piperazine with methyl sulfonyl chloride. The product obtained was characterized by spectroscopic techniques, and the structure was investigated by X-ray crystallography. The compound crystallizes in the monoclinic crystal class in the space group P21/c with cell parameters a=9.5820(4) A, b=16.8150(12) A, c=13.5280(8) A, =127.270(5), and V=1734.5(2)A3 for Z=4. The structure reveals that the piperazine ring is in a chair conformation. There is a large discrepancy around the bond angles of the piperazine N atoms. The geometry around the S atom is distorted tetrahedral.

Full text of DOI:10.1080/15421400701693542

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Synthesis and Crystal Structure
of 1-Benzhydryl-4-Methane-
Sulfonyl-Piperazine
S. Naveen a , M. A. Sridhar a , J. Shashidhara Prasad
a , C. S. Ananda Kumar b , S. B. Benaka Prasad b , N.
R. Thimmegowda b & K. S. Rangappa b
a Department of Studies in Physics , University of
Mysore , Mysore, Mysore, India
b Department of Studies in Chemistry , University of
Mysore , Mysore, India
Published online: 22 Sep 2010.
To cite this article: S. Naveen , M. A. Sridhar , J. Shashidhara Prasad , C. S. Ananda
Kumar , S. B. Benaka Prasad , N. R. Thimmegowda & K. S. Rangappa (2007) Synthesis
and Crystal Structure of 1-Benzhydryl-4-Methane-Sulfonyl-Piperazine, Molecular
Crystals and Liquid Crystals, 474:1, 67-76, DOI: 10.1080/15421400701693542
To link to this article: http://dx.doi.org/10.1080/15421400701693542
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Mol. Cryst. Liq. Cryst., Vol. 474, pp. 67–76, 2007
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421400701693542
Synthesis and Crystal Structure of
1-Benzhydryl-4-Methane-Sulfonyl-Piperazine
S. Naveen
M. A. Sridhar
J. Shashidhara Prasad
Department of Studies in Physics, University of Mysore, Mysore, India
C. S. Ananda Kumar
S. B. Benaka Prasad
N. R. Thimmegowda
K. S. Rangappa
Department of Studies in Chemistry, University of Mysore,
Mysore, India
The title compound, 1-benzhydryl-4-methanesulfonyl-piperazine, was synthesized
by the nucleophilic substitution of 1-benzhydryl-piperazine with methyl sulfonyl
chloride. The product obtained was characterized by spectroscopic techniques,
and the structure was investigated by X-ray crystallography. The compound crys-
tallizes in the monoclinic crystal class in the space groupꢀ P21=c with cell para-
ꢀ
ꢀ
meters a ¼ 9.5ꢀ820(4) A, b ¼ 16.8150(12) A, c ¼ 13.5280(8) A, b ¼ 127.270(5)ꢀ, and
V ¼ 1734.5(2)A3 for Z ¼ 4. The structure reveals that the piperazine ring is in a
chair conformation. There is a large discrepancy around the bond angles of the
piperazine N atoms. The geometry around the S atom is distorted tetrahedral.
Keywords: 1-benzhydryl piperazine; chair conformation; distorted tetrahedron;
nucleophilic substitution
INTRODUCTION
In today’s drug discovery environment, piperazines are one of the most
important building blocks. The epoxide-containing piperazines are
protease inhibitors, which are of use in cardiovascular diseases
[1–3]. Protease inhibitors such as NCO-700 have been used in cancer
Address correspondence to M. A. Sridhar, Department of Studies in Physics, Manasagan-
gotri, University of Mysore, Mysore 570 006, India. E-mail: mas@physics.uni-mysore.ac.in
67

68
S. Naveen et al.
therapy, mainly as antimetastatic agents [4–6]. Unfused aromatic sys-
tems containing piperazine as the terminal substituent have shown
excellent anticancer activity and DNA interaction [7]. They are also
found in antitumor drugs used against colon, prostate, breast, and lung
cancer and leukemia [8]. Chloroalkyl piperazines have shown potent
bioactivity and increased anticancer activity [9]. Bisdioxopiperazines
have been reported for their antitumor effects against two experimental
lung cancer models in vivo [10]. The piperazine analogs have been shown
to have potent antiproliferative activity against colon, prostate, breast,
and lung tumors and leukemia in cell-based assays. Mechanistic evalua-
tions have shown that the piperazines inhibit microtubule synthesis by a
unique mechanism, inhibit cell cycle progression, and inhibit angiogen-
esis, which is critical to a tumor cell’s ability to grow and metastasize.
A literature survey revealed that piperazine derivatives are impor-
tant pharmacophores across a number of different therapeutic areas
[11] and act as antifungal [12], antibacterial, antimalarial, antipsycho-
tic [13], anti-HIV protease [14–16], antidepressant [17], and antitu-
mour agents [8]. Piperazine sulfonamides are among the most
widely used antibacterial [18] agents in the world, chiefly because of
their low cost, low toxicity, and excellent activity against common bac-
terial disease. In continuation of our work on the synthesis of bioactive
heterocycles and their biological evaluation [19–21], the title com-
pound was sythesized. The compound obtained was characterized
spectroscopically and finally confirmed by X-ray crystallography.
EXPERIMENTAL
Melting points were determined using a Selaco650 hot-stage melting-
point apparatus and were uncorrected. The infrared (IR) spectra were
recorded using a Jasco FTIR-4100 series instrument. Nuclear magnetic
resonance (1H NMR) spectra were recorded on a Shimadzu AMX 400
Bruker, 400-MHz spectrometer using dimethylsulfoxide (DMSO) as a
solvent and TMS as internal standard (chemical shift in d ppm). Spin
multiplets are given as s (singlet), d (doublet), t (triplet), dd (doublet
of doublet), and m (multiplet). Mass and purity were recorded on a
LC-MSD-Trap-XCT. Elemental (CHNS) analyses were obtained on
Vario EL III Elementar. Silica-gel column chromatography was per-
formed using Merck 7734 silica gel (60–120 mesh) and Merck thin-layer
chromatography (TLC) plates. The reaction scheme is shown in Fig. 1.
Synthesis of 1-Benzhydryl-4-Bethanesulfonyl-Piperazine
A solution of 1-benzhydryl-piperazine (0.5 g, 1.98 mmol) in dry
dichloromethane was taken and cooled to 0–5ꢀC in an ice bath. Then

1-Benzhydryl-4-methane-sulfonyl-piperazine
69
FIGURE 1 Reaction scheme. Reagents and conditions: 1) NaBH4, methanol,
rt, 5 h 2) thionyl chloride, MDC, 0–5ꢀC, 4 h 3) piperazine, K2CO3, DMF, 80ꢀC,
8 h 4) methane sulfonyl chloride, MDC, triethylamine, rt, 5–6 h.
triethylamine (0.601 g, 5.94 mmol) was added to the cold reaction mix-
ture and stirred for 10 min. Then methyl sulfonyl chloride (0.226 g,
1.98 mmol) was added. The reaction mixture was stirred at room tem-
perature for 5 h. The reaction mixture was monitored by TLC. On com-
pletion of the reaction, the solvent was removed under reduced
pressure, and the residue was taken in water and extracted with ethyl
acetate. Finally a water wash was given to the organic layer and dried
with anhydrous sodium sulphate. The solvent was evaporated to get
the crude product, which was purified by column chromatography over
silica gel using hexane–ethyl acetate (8:2) as an eluent. The pure
product obtained (0.556 g, 85%) was dissolved in ethyl acetate. White
crystals developed after 3 days, due to the slow evaporation of the
solvent. Mp: 192–194ꢀC.
Anal. calcd. for C18H22N2O2S (in %): C, 65.43; H, 6.71; N, 8.48;
1
S, 9.70. Found: C, 65.40; H, 6.68; N, 8.45; S, 9.66. H NMR (DMSO,
400 MHz): d 7.38 (d, 4H, ArꢁH), 7.27 (t, 4H, ArꢁH), 7.15 (t,
2H, ArꢁH), 4.25 (s, 1H, ꢁCHꢁ), 2.92 (bs, 4H, ꢁCH2ꢁ), 2.50 (bs, 4H,
ꢁCH2ꢁ), 2.7 (s, 3H, ꢁCH3ꢁ). IR (KBr, cmꢁ1): 3029, 2959, 2850,
1346, 1285. MS: 331.56. Purity: 99.21.
Crystal Structure Determination
A
single crystal of the title compound with dimensions
0.27 ꢂ 0.25 ꢂ 0.2 mm was chosen for an X-ray diffraction study. The
data were collected on a DIPLabo Image Plate system equipped with

70
S. Naveen et al.
TABLE 1 Crystal Data and Structure Refinement
Parameter
Value
CCDC deposition number
Empirical formula
Formula weight
Temperature
Wavelength
Crystal system
Space group
CCDC 650181
C18H22N2O2S
330.44
293(2) K
˚
0.71073 A
Monoclinic
P21=c
˚
Cell dimensions
a ¼ 9.5820(4) A
˚
b ¼ 16.8150(12) A
˚
c ¼ 13.5280(8) A
b ¼ 127.270(5)ꢀ
3
˚
Volume
1734.5(2) A
Z
4
Density (calculated)
Absorption coefficient
F000
1.265 Mg=m3
0.198 mmꢁ1
704
Crystal size
Theta range for data collection
Index ranges
0.27 ꢂ 0.25 ꢂ 0.2 mm
2.25ꢀ to 25.02ꢀ
ꢁ10 ꢃ h ꢃ 10
ꢁ20 ꢃ k ꢃ 20
ꢁ15 ꢃ l ꢃ 16
Reflections collected
5314
Independent reflections
Absorption correction
Refinement method
Data=restraints=parameters
Goodness of fit on F2
Final R indices [I > 2r(I)]
R indices (all data)
2805 [Rint ¼ 0.0224]
None
Full-matrix least-squares on F2
2805=0=210
1.172
R1 ¼ 0.0395, wR2 ¼ 0.1129
R1 ¼ 0.0484, wR2 ¼ 0.1357
0.023(3)
0.260 and ꢁ0.260 e.A
Extinction coefficient
Largest diff. peak and hole
ꢁ3
˚
a normal focus, 3-kW sealed X-ray source (graphite monochromated
MoKa). The crystal-to-detector distance was fixed at 120 mm with a
detector area of 441 ꢂ 240 mm2. Thirty-six frames of data were col-
lected 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 5ꢀ per minute with an oscillation range of 5ꢀ. Image
processing and data reduction were done using Denzo [22]. The reflec-
tions were merged with Scalepack [23]. All of the frames could be
indexed using a primitive orthorhombic lattice. Absorption correction
was not applied. The structure was solved by direct methods using
SHELXS-97 [24]. Least-squares refinement using SHELXL-97 [25]

1-Benzhydryl-4-methane-sulfonyl-piperazine
71
TABLE 2 Atomic Coordinates and Equivalent Thermal Parameters of the
P P
NonHydrogen Atoms [Ueq ¼ ð1=3Þ
Uijðaꢄi aꢄj Þðai ꢅ ajÞ]
i
j
Atom
x
y
Z
Ueq
N1
C2
C3
N4
C5
C6
S7
08
0.1175(2)
0.2615(3)
0.2723(3)
0.1065(2)
ꢁ0.0305(3)
ꢁ0.0496(3)
0.10797(7)
ꢁ0.0389(2)
0.2784(2)
0.0596(3)
0.1194(3)
0.2581(3)
0.3731(3)
0.4889(3)
0.4911(3)
0.3815(3)
0.2659(3)
ꢁ0.0569(3)
ꢁ0.1255(3)
ꢁ0.2838(4)
ꢁ0.3710(3)
ꢁ0.3052(3)
ꢁ0.1505(3)
0.03334(9)
0.0916(2)
0.1400(2)
0.18145(9)
0.1213(2)
0.0721(2)
ꢁ0.03449(3)
ꢁ0.08436(9)
ꢁ0.0691(1)
0.01452(2)
0.2328(2)
0.2973(1)
0.3144(2)
0.3775(2)
0.4242(2)
0.4072(2)
0.3435(2)
0.2713(2)
0.2662(2)
0.3042(2)
0.3474(2)
0.3521(2)
0.3139(1)
0.3875(2)
0.4410(2)
0.5398(2)
0.4871(2)
0.4410(2)
0.3398(2)
0.29624(5)
0.2564(2)
0.3612(2)
0.1631(2)
0.5809(2)
0.6271(2)
0.7532(2)
0.7967(3)
0.7146(4)
0.5889(3)
0.5452(2)
0.5292(2)
0.5945(2)
0.5494(3)
0.4416(3)
0.3756(3)
0.4183(2)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.0450(4)
.0545(5)
.0534(5)
.0428(4)
.0523(5)
.0524(5)
.0487(2)
.0645(5)
.0709(5)
.0559(5)
.0471(5)
.0496(5)
.0657(7)
.0880(1)
.0930(2)
.0780(8)
.0601(6)
.0472(5)
.0604(6)
.0729(8)
.0732(7)
.0650(6)
.0535(5)
09
C10
C11
C12
C13
C14
C15
C16
C17
C18
C19
C20
C21
C22
C23
with isotropic temperature factors for all the nonhydrogen atoms con-
verged the residual R1 to 0.1674. Subsequent refinements were car-
ried out with anisotropic thermal parameters for nonhydrogen atoms
and isotropic temperature factors for the hydrogen atoms, which were
placed at chemically acceptable positions. The hydrogen atoms were
allowed to ride on their parent atoms. After eight cycles of refinement,
the residual converged to 0.0395. The details of crystal data and
refinement are given in Table 1.y Table 2 gives the atomic coordinates
and equivalent thermal parameters of the nonhydrogen atoms.
Tables 3 and 4 give the list of bond lengths and bond angles, respect-
ively, which are in good agreement with the standard values. The
yCCDC 650181 contains the supplementary crystallographic data for this article.
These data can be obtained free of charge via 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; E-mail: deposit@ccdc.cam.ac.uk

72
S. Naveen et al.
˚
TABLE 3 Bond Lengths (A)
Atoms
Length
N1–C6
N1–C2
N1–S7
C2–C3
C3–N4
N4–C5
N4–C11
C5–C6
S7–O9
1.467(2)
1.475(3)
1.642(2)
1.514(3)
1.465(2)
1.466(2)
1.477(2)
1.513(3)
1.429(2)
1.434(2)
1.768(2)
1.526(3)
1.527(3)
1.390(3)
1.390(3)
1.383(4)
1.371(5)
1.383(5)
1.390(3)
1.388(3)
1.393(3)
1.400(3)
1.369(4)
1.373(4)
1.380(3)
S7–O8
S7–C10
C11–C12
C11–C18
C12–C13
C12–C17
C13–C14
C14–C15
C15–C16
C16–C17
C18–C19
C18–C23
C19–C20
C20–C21
C21–C22
C22–C23
ORTEP of the molecule with thermal ellipsoids drawn at 50%
probability is shown in Fig. 2.
The piperazine ring in the structure adopts a perfect chair confor-
˚
mation with the atoms N1 and N4 deviating 0.216(2) A and
˚
ꢁ0.269(2) A respectively from the least-squares plane defined by the
atoms C2=C3=C5=C6. This is confirmed by the puckering parameters
ꢀ
[26] Q 0.5896(29) A, h 175.18(26)ꢀ, and / 356(4)ꢀ. The ring-puckering
analysis revealed that the piperazine ring has a weighted average ring
ꢀ
bond distance of 1.4832 (16, 98) A and a weighted average torsion
angle of 58.53 (12,119)ꢀ. The conformation of the attachment of the
diphenylmethyl and the sulfonyl groups to the piperazine ring are well
described by the torsion angle values of 169.4(2)ꢀ and ꢁ176.4(2)ꢀ for
S7–N1–C6–C5 and C11–N4–C3–C2 respectively, that is, they adopt
þ antiperiplanar and ꢁantiperiplanar conformations with respect to
one another. The bonds N1–S7 and N4–C11 connecting the sulfonyl
and the diphenylmethyl groups make an angle of 82.71(11)ꢀ and

1-Benzhydryl-4-methane-sulfonyl-piperazine
73
TABLE 4 Bond Angles (ꢀ)
Atoms
Angle
C6–N1–C2
C6–N1–S7
C2–N1–S7
N1–C2–C3
N4–C3–C2
C3–N4–C5
C3–N4–C11
C5–N4–C11
N4–C5–C6
N1–C6–C5
O9–S7–O8
O9–S7–N1
O8–S7–N1
O9–S7–C10
O8–S7–C10
N1–S7–C10
N4–C11–C12
N4–C11–C18
C12–C11–C18
C13–C12–C17
C13–C12–C11
C17–C12–C11
C14–C13–C12
C15–C14–C13
C14–C15–C16
C15–C16–C17
C16–C17–C12
C19–C18–C23
C19–C18–C11
C23–C18–C11
C18–C19–C20
C21–C20–C19
C20–C21–C22
C21–C22–C23
C22–C23–C18
111.7(2)
115.4(2)
116.1(1)
109.5(2)
110.6(2)
107.9(2)
111.0(2)
110.9(2)
110.5(2)
110.1(2)
119.3(1)
107.4(1)
106.6(1)
108.2(1)
107.2(1)
107.6(1)
111.5(2)
111.2(2)
109.5(2)
118.6(2)
119.7(2)
121.6(2)
121.1(3)
119.7(3)
120.3(3)
119.9(3)
120.3(2)
118.3(2)
120.2(2)
121.6(2)
120.0(2)
120.5(2)
119.9(2)
120.0(2)
121.2(2)
74.46(18)ꢀ respectively with the Cremer and Pople plane [26] of the
piperazine ring and thus are in the equatorial plane. The sum of the
bond angles around the piperazine N atoms, N1 ¼ 341.3(2)ꢀ and
N4 ¼ 329.0(2)ꢀ, respectively, indicate that they are sp3 hybridized
and that they adopt a pyramidal geometry.
The two phenyl rings bridged by the central carbon atom is planar
within the experimental limits, and they make a dihedral angle of
75.65(16)ꢀ with each other. The piperazine ring makes an angle of

74
S. Naveen et al.
76.79(15)ꢀ and 78.48(14)ꢀ with the least-squares plane of the two phe-
nyl rings C12 ꢅ ꢅ ꢅ C17 and C18 ꢅ ꢅ ꢅ C23, respectively. These values are com-
parable with the reported values of 76.84(13)ꢀ and 77.55(14)ꢀ reported
for 1-[bis-(4-fluorophenyl)-methyl]-4-methane sulfonyl piperazine [27].
The angular disposition of the bonds about the S atom shows signifi-
cant deviation from that of a regular tetrahedron with the largest
deviations being observed for the O–S–O [O8–S7–O9 ¼ 119.3(1)ꢀ]
and O–S–N [O9–S7–N1 ¼ 107.39(9)ꢀ] angles. This widening of the
=
angles is due to the repulsive interactions between the S O bonds
and the nonbonded interactions involving the two SꢁO bonds and
the varied steric hindrance of the substituents. The structure thus
ꢀ
has less steric interference. The S–N bond distance [1.642(2) A] lies
ꢀ
within the expected range of 1.63–1.69 A. The reduction of the
N1–S7–C10 angle to 107.62(9)ꢀ from the ideal tetrahedral value is attri-
buted to the Thorpe–Ingold effect [28]. The sulfonyl O atoms O8 and
O9 are oriented in þ synclinal and ꢁsynclinal conformations, respect-
ively, as indicated by the torsion angle values of 50.7(2)ꢀ and ꢁ47.2(2)ꢀ
for C2–N1–S7–O9 and C6–N1–S7–O8, respectively. The bond angle
FIGURE 2 ORTEP of the molecule with thermal ellipsoids drawn at 50%
probability.

1-Benzhydryl-4-methane-sulfonyl-piperazine
75
FIGURE 3 Packing of the molecules when viewed down the a axis.
C6–N1–C2–111.7(2)ꢀ is significantly larger than C3–N4–C5 ¼
107.9(2)ꢀ. This difference seems to result from the steric effects of
the sulfonic group attached to the piperazine N atom. The packing
of the molecules when viewed down the a axis indicates that the
molecules are stacked in pairs (Fig. 3).
ACKNOWLEDGMENTS
The authors are grateful to the Department of Science and Technology
and the government of India for financial assistance under Projects
SP=I2=FOO=93 and UGC-SAP (phase I) F.540=10=DRS=2004 (SAP-I).
REFERENCES
[1] Haga, N., Ishibashi, T., Hara, A., & Abiko, Y. (1985). Pharmacology, 31, 208.
[2] Sashida, H. & Abiko, Y. (1985). Biochempharm., 34, 3875.
[3] Toyo-Oka, T., Kamishiro, T., Masaki, M., & Masaki, T. (1982). Japanese Jeart J.,
23, 829.
[4] Berquin, I. M. & Sloane, B. F. (1994). Prospectives in Drug Discovery and Design, 2,
371.
[5] Dimitroff, C. J., Sharma, A., & Bernacki, R. (1998). J. Cancer Invest., 16, 279.
[6] Lah, T. T. & Kos, J. (1998). Biol. Chem., 379, 125.
[7] Wilson, W. D., Henryk, J., Barton, F., Tanious, A., & Kong, S.-B., Strekowski, L.
(1990). Biol. Chem., 35, 227.

76
S. Naveen et al.
[8] Hulme, C. (1999). Tetrahedron Lett., 40, 5295.
[9] Guo, C. C., Li, H. P., & Zhang, X. B. (2003). Bioorg. Med. Chem., 11, 1745.
[10] Lu, D.-Y., Xu, B., & Ding, J. (2004). BMC Pharmacology, 4, 32.
[11] Berkheij, M. (2005). Tetrahedron Lett., 15, 2369.
[12] Upadhayaya, R. S., Sinha, N., Jain, S., Kishore, N., Chandra, R., & Arora, S. K.
(2004). Bioorg. Med. Chem., 12, 2225.
[13] Choudhary, P., Kumar, R., & Verma, K. (2006). Bioorg. Med. Chem., 14, 1819.
[14] Vacca, J. P., Dorsey, B. D., Schleif, W. A., Levine, R. B., McDaniel, S. L., Darke, P.
L., Zugay, J., Quintero, J. C., Blahy, O. M., Sardana, B. B., Schlabach, A. J.,
Graham, P. I., Condra, J. H., Gotalib, L., Holloway, M. K., Lin, J., Chen, I. W.,
Vastag, K., Ostovic, D., Anderson, P. S., Emini, E. A., & Hu, J. R. (1994). J. Med.
Chem., 37, 3443.
[15] Askin, D., Eng, K. K., Rossen, K., Purick, R. M., Wells, K. M., Volante, R. P., &
Reider, P. J. (1994). Tetrahedron Lett., 35, 673.
[16] Rossen, K., Weissman, S. A., Sagar, J., Reamer, A., Askin, D. A., Volante, R. P., &
Reider, P. J. (1995). Tetrahedron Lett., 36, 6419.
[17] Korosi, J., Szabo Nee, C., Gabriella, Lay Nee, K., Erdelyi Nee, P., Lujza, Balla Nee,
K., Bolya, Kiszelly, & Eniko. (1975). EGYT US-3865828.
[18] Ambrose, A. E. & William, J. W. (2003). J. Med. Chem., 44, 3849.
[19] Priya, B. S., Basappa, Nanjunda swamy, S., & Rangappa, K. S. (2005). Bioorg. Med.
Chem., 13, 2623.
[20] Nanjunda swamy, S., Basappa, Sarala, G., Priya, B. S., Gaonkar, S. L., Prasad, J.
S., & Rangappa, K. S. (2006). Bioorg. Med. Chem. Lett., 15, 1811.
[21] Narendra Sharath Chandra, J. N., Sadashiva, C. T., Kavitha, C. V., & Rangappa, K.
S. (2006). Bioorg. Med. Chem., 14, 6621.
[22] Otwinowski, Z. & Minor, W. (1997). In: Methods in Enzymology, Carter, C. W., Jr. &
Sweet, R. M. (Eds.), Academic Press: New York, 276, 307–326.
[23] Mackay, S., Gillmore, C. J., Edwards, C., Stewart, N., & Shankland, K. (1999).
maXus Computer Program for the Solution and Refinement of Crystal Structures,
Bruker Nonius: Delft, The Netherlands.
[24] Sheldrick, G. M. (1997). SHELXS-97: Program for Crystal Structure Solution,
University of Gottingen: Gottingen, Germany.
[25] Sheldrick, G. M. (1997). SHELXL-97: Program for Crystal Structure Solution,
University of Gottingen: Gottingen, Germany.
[26] Cremer, D. & Pople, J. A. (1975). J. Amer. Chem. Soc., B12, 1354.
[27] Naveen, S., Sadashiva, C. T., Narendra Sharath Chandra, J. N., Sridhar, M. A.,
Shashidhara Prasad, J., & Rangappa, K. S. (2007), Mol. Cryst. Liq. Cryst., 469, 89.
[28] Bassindale, A. (1984). The Third Dimension in Organic Chemistry, John Wiley and
Sons: New York, ch. 1, 11.