Preparation and x-ray crystal structure of (2Z,4E)-5-(4-substituted phenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-ones (Curcumin Analogs) from the condensation-elimination of dilithiated 1-benzoylacetone with substituted benzaldehydes

Article abstract of DOI:10.1007/s10870-013-0458-2

1-Benzoylacetone 1 was dilithiated with lithium diisopropylamide or lithium hexamethyl-disilazide, and the resulting dianion type intermediate 1a was condensed with (lithium) 4-hydroxybenzaldehyde, 4-dimethylaminobenzaldehyde, or 4-chlorobenzaldehyde to a

Full text of DOI:10.1007/s10870-013-0458-2

J Chem Crystallogr (2013) 43:629–635
DOI 10.1007/s10870-013-0458-2
ORIGINAL PAPER
Preparation and X-Ray Crystal Structure of (2Z,4E)-5-(4-
substituted phenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-ones
(Curcumin Analogs) from the Condensation–Elimination
of Dilithiated 1-Benzoylacetone with Substituted Benzaldehydes
•
Alton R. Thomas William G. Shuler Ellyn A. Smith Sarah S. Carlisle
•
•
•
•
Shabree L. Knick Andrew J. Puciaty Clyde R. Metz Donald G. VanDerveer
•
•
•
•
Colin D. McMillen William T. Pennington Charles F. Beam
•
Received: 20 December 2012 / Accepted: 3 September 2013 / Published online: 11 October 2013
Ó Springer Science+Business Media New York 2013
Abstract 1-Benzoylacetone 1 was dilithiated with lithium
diisopropylamide or lithium hexamethyl-disilazide, and the
resulting dianion type intermediate 1a was condensed with
(lithium) 4-hydroxybenzaldehyde, 4-dimethylaminobenz-
aldehyde, or 4-chlorobenzaldehyde to afford hydroxyl-b-
diketones that were not isolated but underwent linear dehy-
dration to afford products, (2Z,4E)-5-(4-hydroxyphenyl)-3-
hydroxy-1-phenylpenta-2,4-dien-1-one 2 C17H14O3; (2Z,4E)-
5-(4-(dimethylamino)phenyl)-3-hydroxy-1-phenylpenta-2,4-
dien-1-one 3 C19H19NO2; and (2Z,4E)-5-(4-chlorophenyl)-
3-hydroxy-1-phenylpenta-2,4-dien-1-one 4 C17H13ClO2.
Crystals of C17H14O3 2 are orthorhombic, Pna21, a =
Introduction
Analogs of curcumin are usually associated with alkene b-
diketones or their enol tautomers, dienones, (or related
conjugated systems [reviews 1–3]). They have been
extensively investigated especially with regard to their
syntheses [4–12], characterization [13–18], for preparation
of metal chelates [19–22], and their potential for medical
studies [14, 23]. The value of curcumin analogs has been
reported during the past 20 years for their potential as
anticancer agents [1]; their structure–activity relationships
with different biological activities [2]; as integrase inhibi-
tors anti-HIV agents [3]; for UV/Vis spectral behavior of
selected curcumin analogs [15]; for proton NMR spectro-
scopic investigations of new curcumin analogs [14] and
other uses.
˚
20.937(4) A, b = 11.683(3) A, c = 5.490(1) A, Z = 4,
˚
˚
3
V = 1343.1(5) A , R1 = 0.0478 and wR2 = 0.1143 for
˚
reflections with I [ 2r(I); crystals of C19H19NO2 3 are
˚
monoclinic, P21/c, a = 16.637(3) A, b = 10.736(2) A,
˚
3
˚
˚
c = 9.197(1) A,b = 105.670(5)°,Z = 4, V = 1581.7(5) A ,
R1 = 0.0609 and wR2 = 0.1491 for reflections with I[
2r(I); crystals of C17H13 ClO2 4 are monoclinic, P21/c,
A specific group of these analogues can be prepared
from the condensation of 1-benzoyl-acetone and aromatic
aldehydes. These compounds are candidates for additional
syntheses, spectral studies including X-ray crystal analysis
[23], and biological testing. There is a historical prepara-
tion of some of these compounds reported in 1914 [4].
Nearly five decades later they were prepared by strong base
methods including multiple anions of b-diketones, such as
1-benzoylacetone, undergoing aldol type condensations
with aromatic aldehydes prepared with alkali amides in
liquid ammonia. This would yield hydroxyl b-diketone
intermediates, which could be isolated if desired, and they
could then undergo linear dehydration to afford the alkene
b-diketone system made up of several tautomers [5–8].
There have been several additional different preparative
methods developed [9–12] for these compounds.
˚
˚
˚
a = 31.574(6) A, b = 5.780(1) A, c = 7.423(2) A, b =
94.47(3)°, Z = 4, V = 1350.5(5) A , R1 = 0.0696 and
3
˚
wR2 = 0.2423 for reflections with I [2r(I).
Keywords Multiple anion syntheses Á Curcumin
analogs Á 1-Benzoylacetone Á Benzaldehydes
A. R. Thomas Á W. G. Shuler Á E. A. Smith Á
S. S. Carlisle Á S. L. Knick Á A. J. Puciaty Á
C. R. Metz Á C. F. Beam (&)
Department of Chemistry and Biochemistry,
College of Charleston, Charleston, SC 29424, USA
e-mail: beamc@cofc.edu
Recently, we reported the synthesis of symmetrical
1,3,5-pentanetriones by the condensation of acetone with
select benzoate esters using lithium hexamethyldisilazide
D. G. VanDerveer Á C. D. McMillen Á W. T. Pennington
Department of Chemistry, Clemson University,
Clemson, SC 29634, USA
123

630
J Chem Crystallogr (2013) 43:629–635
O
C
O
C
Li
Li
O
O
O
C
O
C
i
C
C
H5
C6
H
C
3
C
H5
C6
H
2
C
C
H5
C6
H
2
C
C
H2
H
HLi
Li
1a
iii
1
iv
ii
H
O
C
O
H
O
O
H
O
C
O
H
C
H
C
H
C
C
C
C
C
H5
C6
C
H
C
H5
C6
C
C
H5
C6
C
C
H
H
H
H
H
H
C
3
2
H
O
N
3
l
C
4
H
C
3
. and
or
LDA LHMDS
4-hydroxybenzaldehyde
i. diketo taut
1a and
as
-
ii.
iii.
iv.
4 Li
H
H
OC6 4C O
a
1
and 4-dimethylaminobenzaldehyde
a and
1
4-chlorobenzaldehyde
Scheme 1 Synthesis of curcumin analogs 2–4
(LHMDS) for deprotonation and possible complex forma-
tion consisting of a monolithiated acetone, hexamethyldi-
silazide (HMDS), LHMDS and solvent, tetrahydrofuran
[24]. This reaction of acetone, a mono-carbonyl compound,
did not proceed by a dianion reaction path [25]. By com-
parison, a stronger base, lithium diisopropylamide (LDA),
would form a dianion type intermediate with b-diketones
such as 1-benzoylacetone 1. The resulting dilithiated
1-benzoylacetone 1a would selectively react with numer-
ous electrophilic reagents including carbonyl compounds
to afford hydroxyl b-diketone intermediates, Scheme 1,
that can be isolated and have the potential for linear
dehydration to afford alkene b-diketone products, often
referred to as curcumin analogs. Initially, it was unclear
whether LHMDS would be a strong enough base to be used
for similar dilithiation, condensation, and linear dehydra-
tion reactions.
General Procedure
All reagents except for 1-benzoylacetone 1 were prepared
or used in a 5 % molar excess. The procedures employing
LDA or LHMDS are interchangeable. The molar ratio for
the reactants was 1:2:1 for compounds 3 and 4; 1:3:1 for 2
(diketone: base: carbonyl compd.). The reaction was con-
ducted in a flask cooled in an ice bath, fitted with an argon
inlet tube, a pressure equalizing addition funnel and mag-
netic stir bar. To the cooled flask was added via syringe
*13.5 mL (0.021 mol) of 1.6 M n-butyllithium for prep-
aration of 3 and 4; *20 mL (0.0315 mol) of 1.6 M
n-butyllithium for preparation of 2. While stirring, 2.12 g
(0.0210 mol) of diisopropylamine dissolved in 25 mL of
THF was added for preparation of 3 and 4; 3.18 g
(0.0315 mol) for 2; for LHMDS, 3.39 g (0.0210 mol) or
5.08 g (0.0315 mol) HMDS for making LHMDS. The
reaction mixture was stirred for an additional 15 min
before rapid drop wise addition of 1.62 g (0.010 mol)
1-benzoylacetone dissolved in 25 mL of THF during
10 min. The mixture was allowed to dilithiate 1 to 1a for
60 min. The aldehydes (0.0105 mol), dissolved in 25 mL
of THF were added drop wise to the stirred solution 1a
during 10 min. To prepare 3 and 4, the condensation time
was 60 min, and for 2 it was 90 min. The solution/mixture
was neutralized by rapid addition of *100 mL of 3 M
HCl. Solvent grade ether *50–100 mL was added before
the biphasic mixture was cautiously neutralized with solid
sodium bicarbonate to pH *6 (especially important for
product 2), and the two phases were separated. The aque-
ous phase was extracted with ether (2 9 35–50 mL). After
separation the organic layer was washed with brine, dried
with anhydrous calcium chloride, filtered and allowed to
evaporate to either a solid or oil that could be readily re-
crystallized to give products 2–4.
Experimental
All reactions, Scheme 1, were conducted in flame-dried
glassware under an argon atmosphere. Melting points were
determined using a Mel-Temp II melting point apparatus in
open capillary tubes and are uncorrected. 1H NMR
(300 MHz) and 13C NMR (75 MHz) were conducted with a
varian associates 300 MHz NMR spectrometer, and chemi-
cal shifts were recorded in d ppm downfield from an internal
TMS standard. IR spectra were acquired with a Brucker
Alpha-P FT-IR. LC-MS data were obtained from a Thermo-
Finnigan LCQ Advantage system with LCQ Advantage Max
mass spectral detector using electrospray ionization and
direct injection. Tetrahydrofuran (THF) was freshly distilled
from sodium (benzophenone ketyl). All chemicals were
obtained from Aldrich Chemical Co. and/or Alpha Aesar.
123

J Chem Crystallogr (2013) 43:629–635
631
(2Z,4E)-5-(4-hydroxyphenyl)-3-hydroxy-1-phenylpenta-
2,4-dien-1-one (2). Compound 2 was obtained in 44 % yield,
mp 169–171 °C (ethanol/benzene), (lit. mp 183 °C [19]) from
the condensation-dehydration of dianion (1a) with lithium
4-hydroxybenzaldehyde. IR: 3242, 1628, and 1157 cm-1. 1H
NMR (DMSO-d6,): d 6.19 (s, 1H), 6.75 (d, 1H), 7.54–7.70 (m,
9H), 8.03 (d, 1H), and 10.13 (s, OH). 13C NMR (DMSO-d6,): d
97.5, 116.7, 120.7 (CH), 126.5, 127.8, 129.6, 131.0, 133.5,
136.1, 141.3, 160.6, 182.0, and 187.8. LCMS–MS, exact mass,
266.09: (M?H)?, 267.00, (M–H)-, 265.09.
130.0, 132.1, 136.4, 141.3, 151.7, 181.9, and 187.5. LCMS,
exact mass, 293.14: (M?H)?, 294.13.
Single Crystal X-Ray Structure Determination for 3
Dark red crystals of C19H19NO2 3 were recrystallized from a
methanol–water solution in order to give satisfactory crystals
for X-ray determination. Crystal data for X-ray studies were
collected at 183 K using the equipment described above for
compound 2. Data were collected in 0.5° oscillations in x with
20 s exposures. A sweep of data was done using x oscillations
from -70.0° to 90.0° at v = 45° and / = 0.0°; a second
sweep was performed using x oscillations from -70.0° to
90.0° at v = 45° and / = 90.0°. The crystal-to-detector dis-
tance was 26.865 mm. Details of the data collection are
reported in Table 1. The non-hydrogen and hydrogen atoms
were treated as described for compound 2.
Single Crystal X-Ray Structure Determination for 2
Yellow crystals of C17H14O3 2 were recrystallized from
ethanol in order to give satisfactory crystals for X-ray
determination. Crystal data for X-ray studies were col-
lected at 193 K on a Mercury CCD area detector coupled
with a Rigaku AFC8 diffractometer with graphite mono-
chromated Mo-Ka radiation. Data were collected in 0.5°
oscillations in x with 45 s exposures. A sweep of data was
done using x oscillations from -70.0° to 90.0° at v = 45°
and / = 0.0°; a second sweep was performed using x
oscillations from -60.0° to 80.0° at v = 45° and /
= 90.0°. The crystal-to-detector distance was 26.798 mm.
Details of the data collection are reported in Table 1. Data
were collected, processed, and corrected for Lorentz
polarization and for absorption using Crystal Clear (Riga-
ku) [26, 27].
(2Z,4E)-5-(4-chlorophenyl)-3-hydroxy-1-phenylpenta-2,4-
dien-1-one (4). Compound 4 was obtained in 44 % yield, mp
164 °C (chloroform/benzene) from the condensation-dehy-
dration of dianion 1a with 4-chlorobenzaldehyde. IR: 1602,
1273, 1243, 822, and 681 cm-1. 1H NMR (CDCl3): d 6.34 (s,
1H), 6.61 (d, 1H, J = 18 Hz), 7.37 (d, 2H, J = 9 Hz),
7.45–7.56 (m, 5H), 7.63 (d, 1H, J = 18 Hz), 7.93–7.96 (m,
2H). 13C NMR (CDCl3): d 98.1, 124.0, 127.5, 128.8, 129.3,
129.3, 132.8, 133.7, 136.0, 136.3, 138.6, 178.8, and 189.9.
LCMS, exact mass, 284.06: (M?H)?, 285.00.
Single Crystal X-Ray Structure Determination for 4
The non-hydrogen atoms were refined anisotropically.
The hydrogen atoms for C1, C2, C4, and for the rings
containing C6 and C12 (see numbering of atoms in ORTEP
diagram, Fig. 1) were geometrically placed and treated as
Yellow–green crystals of C17H13ClO2 4 were recrystallized
from benzene/chloroform in order to give satisfactory crys-
tals for X-ray determination. Crystal data for X-ray studies
were collected at 193 K using the equipment described
above for compound 2. Data were collected in 0.5° oscilla-
tions in x with 20 s exposures. A sweep of data was done
using x oscillations from -40.0° to 90.0° at v = 45° and /
= 0.0°; a second sweep was performed using x oscillations
from -30.0° to 80.0° at v = 45° and / = 90.0°. The crystal-
to-detector distance was 26.883 mm. Details of the data
collection are reported in Table 1. The non-hydrogen and
hydrogen atoms were treated as described for compound 2.
˚
riding atoms with a C–H bond length of 0.96 A and
U
iso(H) = (1.2) Ueq(parent C atom) and similarly for the
˚
hydrogen atom on O3 using a bond length of 0.84 A. The
hydrogen atom on O1 was located on a difference electron
density map and ideal hydrogen atom coordinates were
likewise used for it. Structure solution, refinement, and the
calculation of derived results were performed using the
SHELX-97 [28] package of computer programs. Neutral
atom scattering factors were those of Cromer and Waber
[29], and the real and imaginary anomalous dispersion
corrections were those of Cromer [29].
(2Z,4E)-5-(4-(dimethylamino)phenyl)-3-hydroxy-1-phe-
nylpenta-2,4-dien-1-one (3). Compound 3 was obtained in
95 % yield, mp 151 °C (ethanol), (lit. mp 108 °C [19]) from
condensation–dehydration of 1a with 4-dimethylamino-
Results and Discussion
During this investigation b-diketone 1 was deprotonated
with LDA or LHMDS to form dilithiated intermediate 1a.
The molecular ratio of the reagents was important: [dike-
tone:base:carbonyl compound], 1:3:1 for 2; and 1:2:1 for 3
and 4. Dianion 1a was separately condensed with (lithium)
4-hydroxybenzaldehyde for 2, or 4-(dimethylamino)benz-
aldehyde for 3, or 4-chloro-benzaldehyde for 4. Upon
1
benzaldehyde. IR: 3100, 2900, 1620, and 1233 cm-1. H
NMR (CDCl3): d 3.04 (s, 6H), 6.29 (s, 1H), 6.47 (d, 1H,
J = 15 Hz), 6.69 (d, 2H, J = 9 Hz), 7.35–7.60 (m, 5H), 7.67
(d, 1H, J = 15 Hz), and 7.94 (d, 2H, J = 9 Hz). 13C NMR
(CDCl3): d 40.2, 96.8, 111.9, 118.1, 122.8, 127.2, 128.6,
123

632
J Chem Crystallogr (2013) 43:629–635
Table 1 Crystallographic data, 2–4
Compound number
2
3
4
CCDC numbera
Color/shape
Dimensions (mm)
Formula
909504
890764
909505
Light yellow/prism
0.65 9 0.26 9 0.24
Dark red/flat plate
0.36 9 0.32 9 0.14
C19H19NO2
293.35
Light yellow–green/tetragonal plate
0.45 9 0.35 9 0.24
C17H13ClO2
284.72
C
17H14O3
Formula mass
T (K)
266.28
193
183
193
Crystal system
Space group
Orthorhombic
Pna21
Monoclinic
P21/c
Monoclinic
P21/c
˚
a (A)
20.937(4)
11.683(3)
5.490(1)
16.637(3)
10.736(2)
9.197(1)
105.670(5)
1,581.7(5)
4
31.574(6)
5.780(1)
7.423(2)
94.47(3)
1,350.5(5)
4
˚
b (A)
˚
c (A)
b (°)
3
˚
V (A )
1,343.1(5)
4
Z
dcalc (g cm-3
)
1.317
1.232
1.400
˚
k (A)
0.71073
0.090
0.71073
0.080
0.71073
0.280
l (mm-1
F(000)
)
560
624
592
h range (°)
Reflections collected
3.40–25.14
10,101
2.98–25.14
14,986
3.58–25.15
4,435
Miller indices
-25 B h B 25
-13 B k B 13
-6 B l B 4
2148
-17 B h B 19
-12 B k B 12
-10 B l B 10
2817
-37 B h B 36
-6 B k B 6
-8 B l B 8
1972
Unique reflections
Unique reflections I [ 2r(I)
Max transmission
Min transmission
Data
1995
2153
1693
1.000
1.0000
1.000
0.834
0.917
0.610
2148
2817
1972
Restraints
1
0
0
Parameters
183
202
182
Final R indices I [ 2r(I)
R1 = 0.0473
wR2 = 0.1153
R1 = 0.0525
wR2 = 0.1230
1.099
R1 = 0.0609
wR2 = 0.1491
R1 = 0.0796
wR2 = 0.1712
1.035
R1 = 0.0696
wR2 = 0.2423
R1 = 0.0791
wR2 = 0.2589
1.190
R indices all data
Goodness of fit on F2
-3
)
˚
Largest diff peak (e A
0.166
0.197
0.315
-3
)
˚
Largest diff hole (e A
-0.207
-0.221
-0.382
a
CCDC 909504 for 2, 890764 for 3, and 909505 for 4 contain the supplementary crystallographic data for this paper. These data can be obtained
free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
neutralization of the respective reaction mixtures with
dilute hydrochloric acid, linear dehydration occurred with
hydroxyl-b-diketone intermediates not being isolated, so as
to afford the tautomeric alkene b-diketone systems 2–4.
The crystalline tautomer isolated is illustrated in Scheme 1.
X-ray single crystal analysis showed the same curcumin,
enol bonding structural features (2Z,4E), and the tautomers
were clearly displayed in the ORTEP diagrams [30] for
each of the curcumin analogs 2–4, Figs. 1, 2, and 3. In
order to obtain satisfactory crystals for analysis, different
solvent or combination systems were used; however, the
same tautomer structural type was obtained for each
product. The structures of products 2–4 were also sup-
1
ported in part by IR, H and 13C NMR, and liquid chro-
matography mass spectrometry (LCMS). For compounds
2–4 the IR spectra gave information that products had
resulted, and displayed dominant absorptions between
1,602 and 1,628 cm-1 resulting from aromatic and
123

J Chem Crystallogr (2013) 43:629–635
633
O2
O1
C3
C13
H
C1
C5
C7
O
C
O
C
C14
C15
C8
H
C
C12
C17
C2
C4
C6
C
H
C
C9
C11
H
O3
C16
C10
O
H
Fig. 1 ORTEP diagram (50 % ellipsoids for non-hydrogen atoms), (2Z,4E)-5-(4-hydroxyphenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-one;
C17H14O3 2, and conventional illustration
O1
C3
C13
O2
C5
H
C1
O
C
O
C
C7
C14
C15
C18
C8
H
C12
C
C6
C
H
C
C2
C4
N1
H
C11
CH3
CH3
C19
C17
C16
N
C9
C10
Fig. 2 ORTEP diagram (50 % ellipsoids for non-hydrogen atoms), (2Z,4E)-5-(4-(dimethylamino)phenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-
one; C19H19NO2 3, and conventional illustration
O1
C3
O2
H
C13
O
C
O
C
C1
C5
C14
C15
C7
H
C
C8
C12
C17
C2
C4
C6
C11
C
H
C
Cl1
H
C9
C16
l
C
C10
Fig. 3 ORTEP diagram (50 % ellipsoids for non-hydrogen atoms), (2Z,4E)-5-(chlorophenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-one; C17H13
ClO2 4, and conventional illustration
probably conjugated vinyl absorptions; 1H NMR displayed
two vinyl protons bonded to C4 and C5 (C1 and C2 OR-
TEP, respectively), d 6.19–6.90 ppm; 13C NMR gave
consistent absorptions, d, for C1 to C5 (Chem. Abstr.
numbering): C1 (C5 ORTEP), 188–190; C2 (C4 ORTEP),
96.8–98.1; C3 (C3 ORTEP), 179–182; C4 (C2 ORTEP),
121–124; and C5 (C1 ORTEP), 139–141 ppm.
C4–C5 bond, and a double C5–O2 bond and a second
tautomer in which there is a double C3–O1 bond, a single
C3–C4 bond, a double C4–C5 bond, and a single C5–O2
bond. The H atom in each tautomer is bonded to either O1
or O2 depending on which O atom is involved in forming
the single C–O bond.
The tautomers shown in Figs. 1, 2 and 3 are consistent
with the slightly different respective bond lengths. This
choice agrees with the results of theoretical molecular
modeling calculations [31] at the B3LYP/6-31G(d) level
on an isolated molecule of each tautomer that indicate the
tautomers shown in the figures are slightly more stable
(*1 kcal mol-1) than the second tautomer. Because there
is a rather small activation energy between these two tau-
tomers (*6 kcal mol-1), both tautomers should be present
The molecular structures of 2–4 are shown in Figs. 1, 2
and 3. Selected bond distances and angles for these com-
pounds 2–4 are listed in Table 2. The nearly equal C3–C4
and C4–C5 bond lengths and the nearly equal C3–O1 and
C5–O2 bond lengths in these compounds indicate that the
crystal probably contains some disorder between two tau-
tomers: the first as shown in Figs. 1, 2 and 3 in which there
is a single C3–O1 bond, a double C3–C4 bond, a single
123

634
J Chem Crystallogr (2013) 43:629–635
˚
deprotonating a b-diketone, 1-benzoylacetone, to give the
dilithiated dianion-type intermediate. This was followed by
its condensation with substituted benzaldehydes, to afford
hydroxyl b-diketone intermediates that were not isolated,
and underwent linear elimination of water to afford the
targeted alkene b-diketone, a curcumin analog. X-ray
crystal analysis was important in showing that the same
tautomer structural features of the easily isolated products
2–4, (2Z,4E)-5-(4-substituted phenyl)-3-hydroxy-1-phe-
nylpenta-2,4-dien-1-ones, could be recrystallized from
common solvents or mixed solvents. All of the molecules
analyzed are essentially planar.
Table 2 Selected bond distances (A) and angles (°), 2–4
Bond
distances
Bond
angles
C1–C12
C1–C2
C2–C3
C3–C4
C4–C5
C5–C6
C3–O1
C5–O2
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
3
3
1.455(4)
1.447(3)
1.470(6)
1.338(4)
1.347(3)
1.337(6)
1.446(4)
1.447(3)
1.452(6)
1.382(4)
1.385(3)
1.374(6)
1.415(4)
1.406(3)
1.414(6)
1.501(4)
1.482(3)
1.490(6)
1.321(4)
1.318(3)
1.322(5)
1.272(4)
1.286(3)
1.264(6)
1.360(4)
1.365(3)
1.741(4)
1.448(3)
1.455(3)
C17–C12–C1
C12–C1–C2
C1–C2–C3
C2–C3–C4
C3–C4–C5
C4–C5–C6
C5–C6–C11
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
2
3
4
123.3(3)
124.4(2)
122.9(4)
126.8(3)
128.9(2)
127.1(4)
123.0(3)
121.6(2)
122.2(4)
121.9(3)
122.9(2)
122.1(4)
121.4(3)
120.7(2)
121.2(4)
120.9(3)
122.2(2)
121.9(4)
122.3(3)
121.6(2)
122.6(4)
Acknowledgments We wish to thank the following sponsors for
support: the Research Corporation, the Summer Undergraduate
Research Forum (SURF) of the College of Charleston, and the
Howard Hughes Medical Institute (HHMI) along with earlier Grants
from the National Science Foundation (CHE # 9708014 and #
0212699) for Research at Undergraduate Institutions (NSF-RUI), and
the United States Department of Agriculture (NRICGP # 2003-35504-
1285).
References
1. Agrawal DK, Mishra PK (2010) Med Res Rev 30:818
2. Lin L, Lee KH (2006) Stud Nat Prod Chem 33:785
3. Gupta SP, Nagappa AN (2003) Curr Med Chem 10:1779
4. Hellthaler T (1914) Justus Liebigs Ann Chem 406:151
5. Hauser CR, Yost RS, Ringler BI (1949) J Org Chem 14:261
6. Linn BO, Hauser CR (1956) J Am Chem Soc 78:6066
7. Hauser CR, Harris TM (1958) J Am Chem Soc 80:6360
8. Light RJ, Hauser CR (1961) J Org Chem 26:1716
9. Bestmann HJ, Saalfrank RW (1976) Chem Ber 109:403
10. Lim D, Zhou G, Livanos AE, Fang F, Coltart DM (2008) Syn-
thesis 13:2148
11. Daniel FF, Zhou G, Coltart DM (2007) Org Lett 9:4139
12. Katritzky AR, Meher NK, Singh SK (2005) J Org Chem 70:7792
13. Radeglia R, Arrieta AF (1998) Pharmazie 53:28
14. Arrieta A, Beyer L, Kleinpeter E, Lehmann J, Dargatz M (1992)
J Prakt Chem 334:696
C15–O3
C15–N1
C15–Cl1
N1–C18
N1–C19
in significant amounts. The only evidence for the disorder
in the sample not being a 50/50 mixture is the two slightly,
but significant, different C–O distances.
15. Dietze F, Arrieta AF, Zimmer U (1997) Pharmazie 52:302
16. Gustav K, Bartsch U, Guenther W, Letsch C (1993) Monatshefte
Chem 124:1177
All of the molecules are essentially planar. In addition to
the intramolecular hydrogen bonding between O1 and O2
in all three compounds, the molecules of 2 form intermo-
lecular hydrogen bonds with two additional molecules. In
the first bond, O2 is bonded to the H atom which is bonded
to O3 on the second molecule and in the second bond, the
H atom on O3 is bonded to O2 on the third molecule.
17. Arrieta AF (1996) Pharmazie 51:216
18. Gustav K, Bartsch U (1991) Monatshefte Chem 122:565
19. Paul M, Venugopalan P, Krishnankutty K (2002) Asian J Chem
14:1335
20. Ummathur MB (2009) Polish J Chem 83:1717
21. Krishnankutty K, Sayudevi P, Ummathur MB (2007) J Indian
Chem Soc 84:518
22. Venugopalan P, Krishnankutty K (1998) J Indian Chem Soc
75:98
23. Arrieta AF, Mostad A (2005) Acta Crystal E61:o3011
24. Knight JD, Metz CR, Beam CF, Pennington WT, VanDerveer
DG (2008) Synth Com 38:2465
Conclusions
25. Hubbard JS, Harris TM (1980) J Am Chem Soc 102:2110
26. Rigaku Corporation (1999) Crystal clear. Rigaku Corporation,
Danvers 01923
27. Jacobson RA (1998) Absorption correction used REQABS v 1.1.
Molecular Structure Corp, College Station, TX
Select curcumin analogs can also be prepared by the strong
base multiple anion procedures, in comparison to different
boric oxide methods, but involving LDA or LHMDS for
123

J Chem Crystallogr (2013) 43:629–635
635
28. Sheldrick GM (1997) SHELX-97, crystallographic computing
system—Windows Version. University of Gottingen, Gottingen
29. Cromer DT, Waber JA (1974) International tables for X-ray
crystallography, Tables 2.2 B and 2.3.1, vol IV. Kluwer Aca-
demic Publisher, Dordrecht
Kitao O, Nakai H, Vreven T, Montgomery Jr JA, Peralta JE, Ogliaro F,
Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN,
Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A,
Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM,
Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J,
Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R,
Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski
VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels
AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ
(2010) Gaussian 09, Revision B.01. Gaussian Inc., Wallingford
30. Farrugia LJ (1997) J Appl Cryst 30:565
31. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA,
Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson
GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF,
Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K,
Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y,
123