Novel synthesis and crystal structures of two a, a0-bis-substituted benzylidene cyclohexanones: 2,6-Bis-2-nitro(benzylidene)cyclohexanone and 2,6-Bis-4-methyl(benzylidene)cyclohexanone

Article abstract of DOI:10.1007/s10870-011-0094-7

Two a,a0-bis-substituted benzylidene cycloalkanones have been synthesized in presence of SnCl₄ and their crystal structures have been determined by means of X-ray diffraction. The bis(para-methyl) derivative, 2,6-bis- 4-methyl(benzylidene)cyclo

Full text of DOI:10.1007/s10870-011-0094-7

J Chem Crystallogr (2011) 41:1305–1309
DOI 10.1007/s10870-011-0094-7
ORIGINAL PAPER
Novel Synthesis and Crystal Structures of Two
0
a, a -bis-Substituted Benzylidene Cyclohexanones:
2,6-Bis-2-nitro(benzylidene)cyclohexanone
and 2,6-Bis-4-methyl(benzylidene)cyclohexanone
Ali Amoozadeh
Grzegorz Dutkiewicz
Firouzeh Nemati Maciej Kubicki
•
Salman Rahmani
•
•
Mehdi Salehi
•
•
Received: 6 December 2010 / Accepted: 15 April 2011 / Published online: 27 April 2011
Ó The Author(s) 2011. This article is published with open access at Springerlink.com
0
Abstract Two a,a -bis-substituted benzylidene cyclo-
alkanones have been synthesized in presence of SnCl and
Introduction
4
their crystal structures have been determined by means of
Bis(substituted-benzylidene) cycloalkanones are very
important synthetic precursors for synthesis of biologically
active pyrimidine derivatives [1, 2]. These compounds
have gained lots of attention due to their uses as agro-
chemical, pharmaceutical, and perfume intermediates and
as liquid crystal polymer units [3–5]. Many of these
methods suffer, however, from side reactions giving the
corresponding products in low yields [6]. Recently some
new kinds of Lewis acids have been used but in some cases
the yields are less than 38% [7]. We have recently
X-ray diffraction. The bis(para-methyl) derivative, 2,6-bis-
4
-methyl(benzylidene)cyclohexanone 1 crystallizes in the
˚
orthorhombic space group Pbca with a = 9.413(2) A,
˚
b = 10.787(2) A, and c = 33.702(5) A, while bis(ortho-
˚
nitro) derivative, 2,6-bis-2-nitro(benzylidene)cyclohexa-
˚
none in monoclinic P2 /n space group with a = 8.482(2) A,
1
˚
˚
b = 13.435(2) A, c = 15.377(3) A, and b = 92.96(2)°.
In both compounds the olefinic bonds are in E-configura-
tion, and the cyclohexyl rings adopt a sofa conformation.
The phenyl rings are not coplanar with the planes of
C=C–C(=O)–C=C fragments; the dihedral angles between
these planes are 14.25(11) and 19.37(11)° in 1 and 60.50(6)
and 63.26(6)° in 2. This twist might be regarded as the
effect of the repulsive interactions between the hydrogen
atoms from phenyl and cyclohexyl rings, and much larger
values in 2 are certainly connected with the presence of
nitro group in ortho-positions of the phenyl ring. It seems
that, because of the lack of specific interactions the close
packing requirements and the van der Waals forces are main
factors determining the crystal packing.
described the use of poly(ethylene) glycol/AlCl as a green
3
0
and reusable system for the synthesis of a, a -bis(substi-
tuted-benzylidene) cycloalkanones [8]. In recent study,
the versatility of SnCl and the environmentally benign
4
nature of ethanol as a green, inexpensive, and accessible
solvent encouraged us to couple them together and study
their utility for aldol condensation. Comparing the other
methods, our synthetic procedure for preparation of dif-
0
ferent a, a -bis(substituted-benzylidene) cyclohexanones
(Scheme 1) provides good yields for a vast variety of
substituted aromatic aldehydes with both electron with-
drawing and electron releasing groups furthermore. Also
the simplicity of operation, lack of unexpected by-products
and mild condition of temperature are the others advanta-
ges of this method [9]. In recent study for the first time we
Keywords Cyclohexanone ꢀ Conformation ꢀ
Crystal packing ꢀ Crystal structure
have used SnCl as a mild, inexpensive and efficient cat-
4
0
alyst for the synthesis of differents a, a -bis(substituted-
A. Amoozadeh ꢀ S. Rahmani ꢀ M. Salehi ꢀ F. Nemati
Department of Chemistry, Faculty of Science,
Semnan University, Semnan, Iran
benzylidene) cycloalkanones (Scheme 1). Use of ethanol
as a green solvent helped us to improve total yields and
this new combination for the first time provided excel-
lent conditions to obtain good single crystals for X-ray
G. Dutkiewicz ꢀ M. Kubicki (&)
Department of Chemistry, Adam Mickiewicz University,
Grunwaldzka 6, 60-780 Pozna n´ , Poland
e-mail: mkubicki@amu.edu.pl
0
studies of some obtained a, a -bis(substituted-benzylidene)
cyclohexanones. Here we report the results of the X-ray
123

1
306
J Chem Crystallogr (2011) 41:1305–1309
and the planar fragment of the cyclohexanone (C7=C6–
C1(=O1)–C2=C14; referred to as C). The appropriate
values are listed in Table 1, and Fig. 3 shows the com-
parison of both the molecules. As it is evident from Fig. 3,
compound 1 is significantly flatter than 2 as a consequence
of the substituents in ortho-positions in 2. In the Cambridge
Structural Database ([12] version 5.31 of November 2009,
updated August 2010) there are 24 compounds of similar,
3
,5-diaryl-6-monosubstituted-cyclohex-2-enone, structure
Scheme 1
(with no additional substituents in the cyclohexanone ring
and on bridging C-atoms). There are no clear trends in the
overall conformation of the molecules. For instance, for the
crystallographic studies for (2E,6E)-2,6-bis(4-methylben-
zylidene)cyclohexanone (1, Scheme 1) and (2E,6E)-2,6-
bis(2-nitrobenzylidene)cyclohexanone (2). Structures of
some similar compounds have been reported earlier, for
instance bis(3-nitro) [10] and bis(4-nitro) derivatives [11].
Interestingly, even for the very similar compounds there
are no indications of isomorphism what can suggest that
very weak interactions are responsible for crystal packing.
0
derivatives with the single substituents at 4,4 positions
the spread of dihedral angles is quite big, the twist between
0
the terminal rings ranges from 0.3° in 4-methyl-4 -nitro
derivative [13] to 51.4° in one of three symmetry-inde-
pendent molecules of 4,4 -dibromo compound [14]. Even
0
in unsubstituted 2,6-bis(benzylidene)cyclohexanone the
angles between the planar fragments are quite large, 38.3°
between the phenyl rings [15]. This lack of coplanarity
which originates from the twist between the aryl rings and
adjacent olefinic groups is regarded as the result of the
repulsive interactions between the hydrogen atoms of the
aryl rings and equatorial hydrogen atoms from cyclohexyl
ring [e.g., 13]. This steric repulsion causes also the increase
in the bond angles at the C-atoms joining the rings i.e.,
C6–C7–C8 and C2–C14–C15 (cf. Table 1). The intra-annular
angles in phenyl rings show the influence of the substitu-
ents (cf. for instance [16]), which is close to additivity in 1
Results and Discussion
Figures 1 and 2 show the perspective views of molecules 1
and 2, respectively. Table 1 lists the relevant bond lengths,
bond angles and torsion angles.
The overall conformation of the molecule might be
described by the dihedral angles between the planar frag-
ments: two phenyl rings, A (C8ꢀꢀꢀC13) and B (C15ꢀꢀꢀC20),
Fig. 1 Anisotropic ellipsoid
representation of the molecule 1
together with atom labeling
scheme [22]. The ellipsoids are
drawn at 50% probability level,
hydrogen atoms are depicted as
spheres with arbitrary radii
Fig. 2 Anisotropic ellipsoid
representations of the molecule
2
together with atom labeling
scheme [22]. The ellipsoids are
drawn at 50% probability level,
hydrogen atoms are depicted as
spheres with arbitrary radii
1
23

J Chem Crystallogr (2011) 41:1305–1309
1307
˚
˚
Table 1 Selected geometrical parameters (A, °). A and B are phenyl
rings (A: C8ꢀꢀꢀC13, B: C15ꢀꢀꢀC20), and C is the planar fragment of the
cyclohexanone (C7=C6–C1(=O1)–C2=C14)
Table 2 Short C–HꢀꢀꢀO contacts geometry (A, °)
D–HꢀꢀꢀA
D–H
HꢀꢀꢀA
DꢀꢀꢀA
D–HꢀꢀꢀA
1
2
1
a
C111–H11CꢀꢀꢀO1
2
0.96
2.57
3.508(3)
165
C1–O1
1.2311(19)
1.336(2)
1.227(2)
1.329(2)
C2–C14
b
C3–H3AꢀꢀꢀO91
0.97
0.97
0.93
0.93
0.93
0.93
0.93
0.93
2.70
2.66
2.60
2.59
2.56
2.75
2.56
2.66
3.620(3)
3.417(3)
3.321(3)
3.429(3)
3.287(3)
3.668(3)
3.476(3)
3.476(3)
159
135
135
151
135
168
168
146
C6–C7
1.345(2)
1.336(2)
c
C5–H5AꢀꢀꢀO1
C2–C1–C6
C1–C6–C7
C6–C7–C8
C1–C2–C14
C2–C14–C15
C4–C3–C2–C14
C4–C5–C6–C7
C1–C2–C14–C15
C1–C6–C7–C8
C2–C14–C15–C20
C6–C7–C8–C9
A/B
118.60(16)
116.48(15)
130.90(16)
117.41(16)
131.69(16)
154.71(17)
118.97(18)
116.21(17)
130.04(18)
116.11(17)
126.69(18)
148.45(19)
-135.4(2)
d
C7–H7ꢀꢀꢀO162
e
C11–H11ꢀꢀꢀO161
e
C12–H12ꢀꢀꢀO91
f
C17–H17ꢀꢀꢀO1
g
C18–H18ꢀꢀꢀO92
h
C20–H20ꢀꢀꢀO162
Symmetry codes
-159.46(17)
-177.06(16)
176.45(16)
27.1(3)
-178.67(18)
175.0(2)
50.2(3)
a
x ? 1/2, y, 3/2 – z
b
c
d
e
f
-x, -y, 1 – z
1
- x, -y, 1 – z
-23.8(3)
-41.7(3)
21.60(10)
60.50(6)
63.26(6)
26.4(3)
1
/2 ? x, ‘ - y, -1/2 ? z
- x, -1/2 ? y, ‘ - z
1/2 ? x, ‘ - y, 1/2 ? z
x, y, 1 ? z
/2 - x, -1/2 ? y, 3/2 - z
5.24(10)
‘
A/C
14.25(11)
19.37(11)
-
B/C
g
h
A/NO
B/NO
2
1
2
10.3(3)
(
substituents in mutual para positions). As expected in case
this latter case. Also the calculations of the least-squares
planes through five ring atoms (C1, C2, C3, C5, and C6)
show that the ring in 2 is more deviated from the ideal sofa
˚
conformation (maximum deviation is 0.064(2) A in 1 and
˚
0.095(2) A in 2). The sixth atom, C5 is significantly out of
of 2 with ortho-substitution the additivity is hardly visible.
In both compounds the olefinic bonds are in E-config-
uration (torsion angles O1–C1–C6–C7 and O1–C1–C2–
C14 are 11.5(2) and -9.0(2)° in 1, and -20.3(3) and
˚
˚
1
2.8(3)° in 2. It might be noted that in both cases the
the mean plane, by 0.729(3) A in 1 and 0.605(3) A in 2.
In the crystal structures virtually no specific interactions
are present. Some potential C–HꢀꢀꢀO contacts are listed in
Table 2. What is quite puzzling, there are also no indica-
tions for either pꢀꢀꢀp or C–Hꢀꢀꢀp interactions which quite
often play significant role in determination of crystal
packing of similar compounds. Therefore, in both the
structures probably the close packing requirements and the
van der Waals contacts determine the packing (Fig. 4).
dihedral angles have opposite signs, as it is in majority—
but not all, actually in 22 out of 31 fragments—structures
from the CSD.
The cyclohexanone rings are in sofa conformations. The
asymmetry parameters [17], which in principle show the
deviation from the ideal symmetry of six-membered ring,
in this case C , have the values of 3.2° in 1 and 8.6° in 2,
what suggests the much more distorted conformation in
2
Fig. 3 Least-squares fit of
molecules 1 and 2; the
cyclohexanone fragments of the
molecules were fitted one onto
another [22]
123

1
308
J Chem Crystallogr (2011) 41:1305–1309
Table 3 Crystal data, data collection, and structure refinement
Compound
1
2
Formula
22
C H
22
O
C
20 16 2 5
H N O
Formula weight
Crystal system
Space group
302.40
364.35
Monoclinic
P2 /n
Orthorhombic
Pbca
1
˚
a (A)
9.413(2)
10.787(2)
33.702(5)
90
8.482(2)
13.435(2)
15.377(3)
92.96(2)
1750.0(6)
4
˚
b (A)
Fig. 4 Fragment of the crystal packing of 1 as seen along x-direction
23]
˚
c (A)
[
b (°)
3
˚
Experimental
V (A )
3422.0(11)
8
Z
3
D (g/cm )
Preparation
1.17
1.38
x
F(000)
1296
760
A mixture of aldehyde (2 mmol) and ketone (1 mmol) and
l (/mm)
h range (°)
hkl range
0.07
0.10
SnCl (0.3 mmol) in EtOH (2 mL) was stirred at 45 °C for
4
3.12–25.00
-11 B h B 7
3.06–25.00
an appropriate time. After completion of the reaction
-10 B h B 9
-15 B k B 9
-18 B l B 17
(
Scheme 2) monitored by TLC), the reaction mixture was
-
-
12 B k B 11
39 B l B 40
cooled in ice bath to precipitate the desired product. Col-
ourless single crystals suitable for X-ray of compounds 1
and 2 were obtained by slow evaporation of an ethanol
solution. 1: Yellow needles: Yield: 89%; mp 171–172 °C;
Reflections
Collected
7696
6293
Unique (Rint
)
3002 (0.017)
1869
3068 (0.030)
1433
-
1
IR (KBr) m: 2938, 2914, 1660, 1600 cm ; 2: Yellow
With I [ 2r(I)
No. of parameters
Weighting scheme
A
needles: Yield: 75%; mp 157–159 °C; IR (KBr) m: 1638,
210
245
-
1
1
617, 1519 cm
.
0.067
0.0381
0.044
Crystallography
R(F) [I [ 2r(I)]
0.047
2
wR(F ) [I [ 2r(I)]
R(F) [all data]
0.114
0.061
Colourless transparent plate-like crystals (0.5, 0.4,
.15 mm; 0.3, 0.3, 0.05 mm for 2) were used for data
0.083
0.114
0
2
wR(F ) [all data]
0.122
0.066
collection. Diffraction data were collected at room tem-
perature by the x-scan technique, on an Xcalibur Eos
diffractometer [18] with graphite-monochromatized MoKa
Goodness of fit
1.014
1.013
3
˚
Max/min Dq (e/A )
0.14/-0.17
0.21/-0.21
˚
radiation (k = 0.71073 A). The data were corrected for
Lorentz-polarization and absorption effects [18]. Accurate
unit-cell parameters were determined by a least-squares fit
of 3533 (1) and 1991 (2) reflections of highest intensity,
chosen from the whole experiment, and then the. Precision
of the diffractometer was also taken into account in order to
avoid unphysically small standard uncertainties [19]. The
structures were solved by direct methods with SIR92 [20]
and refined with the full-matrix least-squares procedure on
2
2 2
SHELXL97 were used. The function Rw(jF j -jF j )
o
2
c
-
1
2
2
was minimized, with w = [r (F ) ? (AP) ] (where
o
2
2
P = [Max (Fo, 0) ? 2Fc ]/3). All non-hydrogen atoms
were refined anisotropically, hydrogen atoms were put in
the calculated positions difference Fourier map, and refined
as a ‘‘riding’’ model with the isotropic displacement
parameters set at 1.2 (1.5 for methyl groups) times the Ueq
value for appropriate non-hydrogen atom. Relevant crystal
data are listed in Table 3, together with refinement details.
2
F by SHELXL97 [21]. Scattering factors incorporated in
Supplementary Material
CCDC-800799 (1) and CCDC-800800 (2) contain supple-
mentary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, by e-mailing data_request@ccdc.cam.
Scheme 2
1
23

J Chem Crystallogr (2011) 41:1305–1309
1309
ac.uk, or by contacting The Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.
7. Watanabe K (1980) Bull Chem Soc Jpn 53:1366
8
9
. Amoozadeh A, Nemati F (2009) S Afr J Chem 62:44
. Motiur Rahman AFM, Jeong B-S, Kim DH, Park JK, Lee ES,
Jahng Y (2007) Tetrahedron 63:2426
Acknowledgment We thank Semnan University for supporting this
study.
1
0. Li Z-H, Li J-J, Wang P (2007) Z Kristallogr New Cryst Struct
22:73
2
1
1
1
1. Quail JW, Das U, Dimmock JR (2005) Acta Cryst E61:o1150
2. Allen FH (2002) Acta Cryst B58:380
3. Quail JW, Doroudi A, Pati HN, Das U, Dimmock JR (2005) Acta
Cryst E61:o1795
4. Zhou LY (2007) Acta Cryst E63:o3113
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
1
1
5. Jia Z, Quail JW, Arora VK, Dimmock JR (1989) Acta Cryst
C45:285
1
1
6. Domenicano A, Murray-Rust P (1979) Tetrahedron Lett 24:2283
7. Duax WL, Norton DA (1975) Atlas of steroid structures. Plenum,
New York, pp 16–22
References
1
8. Oxford Diffraction (2009) CrysAlis PRO (version 1.171.33.36d).
Oxford Diffraction Ltd, Oxfordshire
9. Herbstein FH (2000) Acta Cryst B56:547
0. Altomare A, Cascarano G, Giacovazzo C, Gualardi A (1993) J
Appl Cryst 26:343
1. Sheldrick GM (2008) Acta Cryst A64:112
2. Siemens (1989) Stereochemical workstation operation manual,
Release 3.4. Siemens Analytical X-ray Instruments Inc., Madi-
son, Wisconsin
3. Macrae CF, Bruno IJ, Chisholm JA, Edgington PR, McCabe P,
Pidcock E, Rodriguez-Monge L, Taylor R, van de Streek J, Wood
PA (2008) J Appl Cryst 41:466
1
. Guilford WJ, Shaw KJ, Dallas JL, Koovakkat S, Lee W, Liang A,
Light DR, McCarrick MA, Whitlow M, Ye B, Morrissey MM
1
2
(1999) J Med Chem 42:5415
2
3
. Deli J, L o´ r a´ nd T, Szab o´ D, F o¨ ldesi A (1984) Pharmazie 39:539
. Dimmock JRA, Padmanilayam MP, Zello GA, Nienaber KH,
Allen TM, Santos CL, Clercq E, De Balzarini J, Manavathu EK,
Stables JP (2003) Eur J Med Chem 38:169
2
2
4
5
. Gangadhara KK (1995) Polymer 36:1903
. Artico M, Di Santo R, Costi R, Novellino E, Greco G, Massa S,
Tramontano E, Marongiu ME, De Montis A, La Colla P (1998) J
Med Chem 41:3948
2
6
. Nakano T, Irifune S, Umano S, Inada A, Ishii Y, Ogawa M
(1987) J Org Chem 52:2239
123