Structural studies of seven homoisoflavonoids, six thiohomoisoflavonoids, and four structurally related compounds

Article abstract of DOI:10.1007/s11224-011-9860-6

¹H and ¹³C NMR chemical shifts have been determined and assigned based on PFG ¹H, ¹³C HM...C, and HMBC experiments for 3-(4'-X-benzyl)-4-chromenones (Ia, X = CN and Ib, X = NO ₂), 3-(4'-X-benzyl)-4-th

Full text of DOI:10.1007/s11224-011-9860-6

Struct Chem (2012) 23:209–217
DOI 10.1007/s11224-011-9860-6
ORIGINAL RESEARCH
Structural studies of seven homoisoflavonoids, six
thiohomoisoflavonoids, and four structurally related compounds
•
Arto Valkonen Katri Laihia Erkki Kolehmainen
•
•
•
Reijo Kauppinen Pal Perjesi
´
´
Received: 15 April 2011 / Accepted: 9 August 2011 / Published online: 24 August 2011
Ó Springer Science+Business Media, LLC 2011
Abstract 1H and 13C NMR chemical shifts have been
determined and assigned based on PFG 1H, 13C HMQC, and
HMBC experiments for 3-(40-X-benzyl)-4-chromenones
(Ia, X = CN and Ib, X = NO2), 3-(40-X-benzyl)-4-thio-
chromenones (IIa, X = Cl and IIb, X = Br), (E)-3-(40-X-
benzylidene)-4-chromanones (IIIa–IIIe, X = OCH3, CH3,
Cl, N(CH3)2, Br), (Z)-3-(40-X-benzylidene)4-thiochroma-
nones (IVa–IVd, X = Cl, Br, F, OCH3), 2-benzyl-1,2,3,
4-tetrahydro-1-naphthol (V), 2-benzyl- and (E)-2-benzyli-
dene-1-tetralones (VI and VII), and (E)-2-benzylidene-1-
benzosuberol (VIII). The crystal structures have been
determined for the following seven compounds: derivatives
of 4-chromanones (IIIa–IIId), 1-tetrahydronaphtol (V), and
1-tetralones (VI and VII). The molecular features and
intermolecular interactions in crystal state have been
discussed.
Keywords Homoisoflavonoid ꢀ Thiohomoisoflavonoid ꢀ
NMR ꢀ Single crystal X-ray structure
Introduction
Homoisoflavonoids belong to a large group of naturally
occurring oxygen heterocycles, which have been extracted
among others from the bulbs of Eucomis, Muscari, and
Bellevalia genus (Liliaceae) [1–4]. These plants are eth-
nomedicinally important as the isolated homoisoflavonoid
compounds have excreted antimutagenic and anticlasto-
genic properties. Accordingly, isolation of natural repre-
sentatives [5–10] and synthesis of their analogues [11] are
intensive fields of research due to the great pharmacological
importance of the compounds. Earlier several derivatives
have been synthesized to evaluate their structure-to-anti-
proliferative activity. Molecular modeling revealed differ-
ences in shapes of representative molecules which were
supposed to contribute to the variation in the observed
1
cytotoxic potencies [12]. In this work H and 13C NMR
This article is dedicated to the memory of Prof. emer. Jaakko
Paasivirta (1931–2011), a friend and colleague, whose contributions
to early steps in NMR chemistry in Finland and later to environmental
chemistry and toxicology were outstanding. Also, his devotion to
research issues was exemplary.
chemical shifts are presented for several homoisoflavonoid
derivatives of four subgroups: 3-benzyl-2-chromen-4-one
(Ia, Ib), 3-benzyl-2-thiochromen-4-one (IIa, IIb), (E)-3-
benzylidene-4-chromanone (IIIa–IIIe), (Z)-3-benzylidene-
4-thiochromanone (IVa–IVd) and four structurally related
compounds: 2-benzyl-1,2,3,4-tetrahydro-1-naphthol (V),
2-benzyl- and (E)-2-benzylidene-1-tetralones (VI, VII), as
well as (E)-2-benzylidene-1-benzosuberol (VIII). The
obtained NMR data can be related with the electron
densities in these molecules [13, 14] which further are
connected with their biological and physiological activity
[12, 15, 16]. Single crystal X-ray diffraction was attempted
for all structures, but only for compounds IIIa–IIId and
V–VII the structures were obtained.
Electronic supplementary material The online version of this
article (doi:10.1007/s11224-011-9860-6) contains supplementary
material, which is available to authorized users.
A. Valkonen (&) ꢀ K. Laihia ꢀ E. Kolehmainen ꢀ R. Kauppinen
¨ ¨
Department of Chemistry, University of Jyvaskyla,
¨ ¨
P.O. Box 35, FI-40014 Jyvaskyla, Finland
e-mail: arto.m.valkonen@jyu.fi
´
P. Perjesi
Institute of Pharmaceutical Chemistry, University of Pecs,
´
´
P.O. Box 99, Pecs 7002, Hungary
123

210
Struct Chem (2012) 23:209–217
Experimental
Chemistry
remaining compounds have been described previously
(I–IV: [12, 17, 18]; VI: [19], VII: [15]) and had melting
points in accord with the literature values. The structures of
the investigated compounds and their numbering used are
shown in Fig. 1.
Melting points were determined on a Boetius apparatus and
are uncorrected. Column chromatography was performed
on Kieselgel 60 (0.063 0.2 mm) (Merck) using toluene
as eluent. The progress of the reactions, as well as the
purity of the compounds, was checked by thin-layer chro-
matography (TLC) performed on Kieselgel 60 F254 plates
(Merck) using toluene:ethanol (4:1, v/v) as developing
system. Elemental analyses performed at the Organic
Syntheses of compounds
Compounds I–IV were prepared by condensation of chro-
man-4-one or 1-thiochroman-4-one with various substi-
tuted benzaldehydes using piperidine as the catalyst based
on previously published methods [12, 17]. Briefly, a mix-
ture of chroman-4-one or 4-thiochromanone (10 mmol),
substituted benzaldehyde (10 mmol), and piperidine (five
drops) was heated at 105 °C for 1 h. The solidified residue
´
¨
¨
Chemistry Department of Eotvos Lorand University
(Budapest, Hungary) were undertaken on IIa, IVc, V, and
VIII and were within 0.4% of the calculated values. The
Fig. 1 The structures and
numbering of investigated
compounds
123

Struct Chem (2012) 23:209–217
211
was dissolved in chloroform, washed free of base with
water, dried, and evaporated in vacuo. The residue was
subjected to column chromatography (silica gel/toluene).
The chromatographically pure compounds (I and III; II
and IV) were further purified by crystallization.
data were collected at 173 2 K with a Bruker-Nonius
KappaCCD diffractometer equipped with APEXII detector
using graphite monochromatized MoKa radiation
˚
(k = 0.71073 A). Data were processed with DENZO-SMN
[27]. The structures were solved by direct methods, using
SIR-2002 [28], and refined on F2, using SHELXL-97 [29].
The final refinement cycles for IIIa were performed with
HKLF5/BASF method to solve the observed non-merohe-
dral twinning and TwinRotMat routine of PLATON [30]
was used to generate the HKLF5 reflection file. The
reflections were corrected for Lorenz polarization effects
and absorption correction was not used. The H atoms
bonded to C atoms were calculated to their idealized
positions with isotropic temperature factors (1.2 or 1.5
times the C atom temperature factor) and refined as riding
atoms. The H atoms bonded to O atoms in V were found
(E)-2-Benzylidene-1-tetralone (VII) and its seven-
membered analogue, (E)-2-benzylidene-1-benzosuberone
were synthesized as previously published [15]. Compound
VI was obtained by hydrogenation of VII in methanol with
10% Pd/C catalyst for 1 h [20]. 2-Benzyl-1,2,3,4-tetrahy-
dro-1-naphtol (V) was obtained by standard sodium boro-
hydride reduction of VI. Compound VIII was obtained by
similar sodium borohydride reduction of (E)-2-benzyli-
dene-1-benzosuberone. Each compound was purified by
column chromatography (silica gel, toluene (VI, VII) or
toluene/ethyl acetate = 1:1 (V, VIII)). The melting points
(uncorrected) of the unreported compounds were as fol-
lows: IIa: 105–107 °C (methanol), IVc: 103–105 °C
(methanol), V: 117–119 °C (hexane), VIII: 94–96 °C
(hexane).
˚
from electron density map and fixed to distances of 0.84 A
from O atom with isotropic temperature factor (1.5 times
the O atom temperature factor). The figures were drawn
with ORTEP-3 [31] and MERCURY [32]. Other experi-
mental X-ray data are shown in Table 1. CCDC-746342
(IIIa), CCDC-746343 (IIIb), CCDC-746344 (IIIc),
CCDC-746345 (IIId), CCDC-812985 (V), CCDC-812986
(VI), and CCDC-812987 (VII) contain the supplementary
crystallographic data for this paper. These data can be
obtained free of charge at http://www.ccdc.cam.ac.uk/
conts/retrieving.html [or from the Cambridge Crystallo-
graphic Data Centre (CCDC), 12, Union Road, Cambridge
CB2 1EZ, UK; fax: ?44 1223 336033].
NMR spectroscopy
1
The one-dimensional H and 13C as well as two-dimen-
sional PFG [21] 1H, 1H COSY [22, 23], PFG 1H, 13C
1
HMQC [24, 25], and PFG H, 13C HMBC [26] spectra
were recorded for 0.5 M CDCl3 solution in a 5 mm sample
tube at 30 °C on a Bruker Avance DRX 500 spectrometer
1
working at 500.13 MHz for H and 125.77 MHz for 13C,
1
respectively. In H NMR experiments the number of data
points was 64 K giving a spectral resolution of 0.05 Hz, the
number of scans was 8 and the flip angle 30°. An expo-
nential window function of the spectral resolution was used
prior to FT. The 1H NMR chemical shifts are referenced to
the signal of residual CHCl3 (d = 7.26 ppm from internal
TMS). In 13C experiments the number of data points was
32 K giving a spectral resolution of 0.5 Hz, the number of
scans was 64 and flip angle 30°. A composite pulse
decoupling, waltz-16, was used to remove proton cou-
plings. An exponential window function of the spectral
resolution was used prior to FT. The 13C NMR chemical
shifts are referenced to the center peak of the solvent
Results and discussion
Earlier we have reported syntheses and H and 13C NMR
1
spectral data of a systematically substituted (E)-2-benzy-
lidene-1-benzocyclanones [13–16] and (E)-3-benzylidene-
4-chromanones [12]. As a continuation of this series of
studies, synthesis of (Z)-3-arylidene-4-thiochromanones
(IVa–IVd) is now performed and their stereochemistry
compared with the related (E)-3-arylidene-4-chromanones
(IIIa–IIIe). During the piperidine catalyzed synthesis of
series III and IV an exo–endo double bond migration is
possible and formation of a mixture of (E)-3-arylidene-4-
chromanones (III) and (Z)-3-arylidene-4-thiochromanones
(IV), as well as the respective 3-benzyl-2-chromen-4-ones
(homoisoflavones) (I) and 3-benzyl-2-thiochromen-4-ones
(II) can be observed. According to the previous observa-
tions formation of the respective benzyl derivatives were
found to be the most expressed in the case of using aro-
matic aldehydes with electron withdrawing groups in the
4-position [11]. Separation of the formed exo–endo pairs
could be conveniently accomplished by column chroma-
tography. Investigation of biologic actions of the related
CDCl3 (d = 77.0 ppm from internal TMS). In PFG 1H, 13
C
HMQC, and HMBC measurements the numbers of data
1
points were 1024 (f2 = H) 9 256 (f1 = 13C). This matrix
was zero filled to 2048 9 512 and apodized by a shifted
sine bell window function along both axes prior to FT.
Single crystal X-ray analysis
The crystals suitable for single crystal X-ray diffraction
analyses were obtained by spontaneous evaporation of
CDCl3 from capped NMR sample tubes. The structural
123

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Struct Chem (2012) 23:209–217
Table 1 Selected crystallographic parameters for IIIa–IIId, V, VI, and VII
IIIa
IIIb
IIIc
IIId
V
VI
VIIb
Empirical formula
Formula weight
Crystal system
Space group
C17H14O3
266.28
C17H14O2
250.28
C16H11ClO2
270.70
C18H17NO2
279.33
C17H18
238.31
O
C17H16
O
C17H14
O
236.30
234.28
Triclinic
P-1
Monoclinic
Pc
Monoclinic
P21/n
Monoclinic
Pc
Triclinic
P-1
Monoclinic
C2/c
Monoclinic
P21/c
˚
a (A)
7.5710(5)
12.3844(10)
14.4898(12)
82.855(4)
87.258(5)
75.805(4)
1306.67(17)
4 (2)
14.5493(4)
11.5169(3)
19.7493(5)
90
3.9093(2)
27.6681(12)
11.5091(6)
90
7.6267(2)
15.2911(3)
12.1024(2)
90
9.2398(4)
12.4152(6)
13.2214(6)
63.426(3)
78.614(3)
78.142(3)
1317.83(10)
4 (2)
22.4725(15)
9.7061(6)
14.8703(9)
90
8.9642(3)
16.0541(6)
8.6876(3)
90
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
Volume (A )
Z (Z0)
129.610(2)
90
96.231(3)
90
91.1800(10)
90
127.584(4)
90
103.018(2)
90
3
˚
2549.45(12)
8 (4)
1237.50(11)
4
1411.09(5)
4 (2)
2570.4(3)
8
1218.12(7)
4
Reflections collected/Rint
Data/restraints/parameters
Goodness-of-fit on F2
R1 [I [ 2r(I)]
4551/–a
15416/0.1079 6891/0.0821
8602/0.0528
2490/0/379
1.060
8161/0.0782
7571/0.0707
7422/0.0709
2144/0/163
1.105
4551/0/362
1.132
4498/2/689
1.065
2178/0/172
1.142
4632/112/383 2272/0/163
1.080
1.046
0.0899
0.0654
0.0715
0.0399
0.0829
0.1665
0.0817
0.2053
0.0583
wR2 (all data)
˚
Largest diff. peak/hole eA
0.2177
0.1431
0.1338
0.0876
0.1099
-3
0.339/-0.283 0.232/-0.217 0.413/-0.216 0.144/-0.180 0.210/-0.199 0.459/-0.449 0.157/-0.190
a
Before HKLF5 refinement Rint = 0.0610
b
Same as the 2-benzylidene-1-tetralone structure found from CSD with code name BZTETO [51]
(E)-2-benzylidene-1-benzocyclanones [13–16] indicated
importance of spatial arrangement of the three structural
units of the compounds. In order to have a better under-
standing of the structure-to-stereochemistry relationship
some reduced (V, VI) derivatives of (E)-2-benzylidene-1-
tetralone (VII) were prepared. For comparison, a reduced
derivative (VIII) of the respective (E)-2-benzylidene-1-
benzosuberone was also synthesized for spectroscopic
investigations.
C3’s are 13.1 ppm more shielded in compounds II. Other
13C NMR chemical shift differences are 10 ppm at highest
[33]. Correspondingly in III and IV series C2’s are from
38.1 to 39.1 ppm and C8a’s from 20.2 to 19.7 ppm more
deshielded in oxygen derivatives (III), while other shift
differences are 10.7 ppm at highest. In fully conjugated
systems, (E)-3-benzylidene-4-chromanones (III) and (Z)-3-
benzylidene-4-thiochromanones (IV) the p-substituent has
little effect on the C3 shifts.
The 1H and 13C NMR chemical shifts for all the studied
compounds are presented in Tables 2 and 3, respectively.
1H and 13C NMR data for several structurally close com-
pounds are found also in the literature [1, 6, 9, 16, 33, 34].
The crystal structure of (E)-3-benzylidene-4-chroma-
none was published in 1987 by Katrusiak et al. [35] and our
structural search showed that since then nine substituted
derivatives [36–44] of it have been added to Cambridge
Structural Database (CSD) [45]. The crystallographic dia-
grams for four new derivatives IIIa–IIId are presented in
Fig. 2. As can be seen from Fig. 2 and Table 1 three of
these structures show more than one molecule in asym-
metric unit, as also found with 5,6-benzoderivative [41].
None of these new structures show similar unit cell
parameters to known ones or to each other, i.e. they are not
crystallographically isostructural to any 3-benzylidene-4-
chromanone derivatives. The crystals of IIIa were
observed to be non-merohedrally twinned. The obtained
BASF parameter with HKLF5 refinement was 0.24 defin-
ing the ratio of the two twin domains. In the lack of strong
hydrogen bonding interactions in IIIa–IIId several weaker
forces determine the packing of the crystals. These forces
include C–HꢀꢀꢀO and C–Hꢀꢀꢀp contacts, as well as pꢀꢀꢀp and
1
The greatest H NMR chemical shift differences in series
I and II, 3-benzyl-2-chromen-4-ones and thio-4-chrome-
nones, can be seen in H2, from 0.33 to 0.38 ppm and in H5,
from 0.36 to 0.39 ppm. In other protons (H6, H7, H8, H3a)
the shift differences are much smaller being 0.16 ppm at
highest. In (E)-3-benzylidene-4-chromanones (III) and
(Z)-3-benzylidene-4-thiochromanones (IV), the greatest 1H
NMR chemical shift differences are between H2 and H8
varying from 1.15 to 1.38 ppm and from 0.32 to 0.37 ppm,
respectively.
Comparing 13C NMR chemical shifts of compounds
I and II, former including oxygen and latter a sulfur con-
taining ring, the greatest differences are seen in C2, C3,
and C8a. C2 are from 18.8 to 18.9 ppm and C8a’s from
19.2 to 19.4 ppm more deshielded in compounds I, while
123

Struct Chem (2012) 23:209–217
213
Table 2 1H NMR chemical shifts (ppm) in 0.5 M CDCl3 solution at 30 °C
Compound
H2
H5
H6
H7
H8
H3a
H20, H60
H30, H50
Ia
7.77
7.81
7.43
7.44
5.37
5.36
5.31
5.44
5.29
4.08
4.06
4.08
4.14
8.18
8.20
8.56
8.57
8.02
8.03
8.02
8.02
8.01
8.20
8.19
8.19
8.18
7.37
7.40
7.51
7.53
7.06
7.07
7.08
7.05
7.07
7.26
7.26
7.24
7.24
7.64
7.67
7.56
7.58
7.47
7.48
7.50
7.45
7.49
7.41
7.40
7.39
7.37
7.42
7.44
7.55
7.57
6.96
6.96
6.97
6.95
6.96
7.32
7.31
7.30
7.29
3.83
3.89
3.95
3.94
7.83
7.86
7.81
7.83
7.77
7.71
7.68
7.71
7.74
7.41
7.48
7.21
7.16
7.28
7.22
7.25
7.26
7.17
7.34
7.26
7.37
7.37
7.49
8.14
7.27
7.43
6.97
7.26
7.43
6.73
7.57
7.43
7.57
7.12
6.95
Ib
IIa
IIb
IIIaa
IIIbb
IIIc
IIIdc
IIIe
IVa
IVb
IVc
IVdd
Compound
H1
4.43
H2
H2a
H3
H4
H5
H6
H7
H8
H9
Ve
2.00
2.69
3.03
2.46
3.45
2.61
7.87
6.62
1.93
1.45
2.05
1.72
3.11
2.88
2.58
2.73
2.68
2.85g
2.85g
2.93
1.80j
1.80j
7.04
7.15
7.16
7.18
7.25
7.46
-
VIf
-
7.39
8.05
-
VIIh
VIIIi
-
-
7.23
3.18
2.80
7.47
7.09
7.35
7.16k
8.13
7.18
-
5.31
-
7.41
a
b
c
d
e
OCH3 = 3.86 ppm;
f
CH3 = 2.41 ppm;
N(CH3)2 = 3.04 ppm;
OCH3 = 3.84;
g
H20, H60 = 7.18 ppm, H30, H50 = 7.27 ppm,
h
H40 = 7.18 ppm; H20, H60 = 7.19 ppm, H30, H50 = 7.26 ppm, H40 = 7.18 ppm; between 2.8 and 2.9 ppm; H20, H60 = 7.43 ppm, H30,
H50 = 7.40 ppm, H40 = 7.33 ppm; H20, H60 = 7.16 ppm, H30, H50 = 7.26 ppm, H40 = 7.17 ppm; between 1.84 and 1.77; between 7.18
and 7.15 ppm
i
j
k
hydrophobic interactions (see Electronic Supplementary
Material, of this article for more details). For example, one
pꢀꢀꢀp interaction was found in asymmetric unit of IIIa
result of intermolecular contacts in molecular level is the
spatial orientation of benzylidene group. The planes
formed by phenyl rings C10–C60 and C4a–C8a in IIIa show
angle values close to value 59.1(4)° (Table 4) observed for
unsubstituted 3-benzylidene-4-chromanone [35]. 3-Benzy-
lidene-8-methoxy-6-methylchroman-4-one [39] shows also
similar value of 59.67(4)°. In IIIb–IIId these values are
slightly smaller (46°–55°) as also in several 3-benzylidene-
4-chromanone derivatives [37, 38, 40–44]. 3-Benzylidene-
6-methoxychroman-4-one [36] shows value of 67.78(3)°
for this angle and is the only one significantly larger.
Carbon C2 is on the same side of the C4a–C8a-plane as C20
in all 3-benzylidene-4-chromanone derivatives.
˚
(Fig. 2) with centroid-to-centroid distance of 3.86 A and
˚
closest carbon-to-carbon distance of 3.387(7) A. Although,
these interactions and existing non-specific dispersive for-
ces are weak, they are strong enough to force independent
molecules during crystallization to different conformations
and deviating surroundings, which appear as multiple
molecules in asymmetric unit in the cases of IIIa, IIIb, and
IIId.
The pyrone ring is not planar, as previously observed
[35], and the carbon C2 has the largest offset from the
plane defined by the adjacent benzene ring. The dihedral
angle C8a–O1–C2–C3 (Fig. 1, Table 4) is rather close to
50° in all molecules of IIIa–IIId and have rather similar
angle values in previously known derivatives (38°–54°)
[35–44]. The positive or negative angles show that C2 is on
the left (?) or right (-) side viewed along the plane from
aromatic end and carbonyl on top. In IIIa, IIIb, and IIId
these deviating envelope conformations of pyrone rings
between independent molecules in asymmetric unit are also
a result of influence of intermolecular forces. Another
These crystallographic data do not correspond well with
the previous molecular modeling data of IIIa–IIId [12]
concerning the spatial orientation of C10–C60 benzene ring
and especially the C3–C3a–C10–C20 and C3–C3a–C10–C60
dihedral angles. In modeled structures the angle values
were found to be around 130° and 50°, while in crystal
structures the observed values (Table 4) were closer to
150° and 30° for all molecules in IIIa–IIId. This deviation
arises most probably from inadequate intermolecular force
parameters in molecular modeling. Substituents in position
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Struct Chem (2012) 23:209–217
Table 3 13C NMR chemical shifts (ppm) in 0.5 M CDCl3 solution at 30 °C
Compound C2
C3
C3a
C4
C4a
C5
C6
C7
C8
C8a
C10
C20, C60 C30, C50 C40
CH3
Iaa
153.0 123.0
153.1 123.1
134.2 136.1
134.2 136.1
32.0 177.0 123.7 125.8 125.1 133.7 118.0 156.4 144.6 129.5
31.8 177.1 123.8 125.9 125.3 133.8 118.1 156.5 146.7 129.6
37.2 178.8 131.5 129.0 127.5 131.0 126.4 137.1 137.3 130.6
37.4 178.9 131.6 129.1 127.6 131.1 126.5 137.2 137.9 131.1
132.2
123.7
128.7
131.7
114.3
129.5
129.1
111.7
132.0
129.1
132.0
115.9
114.3
110.3
146.7
132.3
120.4
-
-
-
-
Ib
IIa
IIb
IIIa
IIIb
IIIc
IIId
IIIe
IVa
IVb
IVcb
IVd
67.8 128.9 137.2 182.1 122.1 127.9 121.8 135.6 117.8 160.7 127.0 132.0
67.7 130.1 137.5 182.2 122.1 127.9 121.8 135.7 117.8 161.1 131.6 130.1
67.5 131.5 136.0 181.9 121.9 128.0 122.0 136.0 117.9 161.1 135.6 131.2
68.2 126.1 138.2 182.0 122.2 127.8 121.6 135.2 117.6 160.8 122.4 132.5
67.4 131.5 135.9 181.8 121.9 127.9 122.0 135.9 117.9 161.1 133.2 131.3
29.2 133.5 136.2 185.6 132.3 130.5 125.9 133.1 127.9 141.0 133.5 130.8
29.2 133.6 136.2 185.6 132.3 130.5 125.9 133.1 127.9 141.0 133.9 131.0
29.1 132.8 136.3 185.6 132.3 130.4 125.8 133.0 127.8 140.9 131.0 131.4
29.4 131.0 137.7 185.8 132.6 130.4 125.8 132.8 127.9 140.9 127.5 131.4
161.0 55.4
139.9 21.4
132.8
–
151.1 40.0
123.8
135.0
123.2
162.8
–
–
–
–
160.3 55.4
Compound C1
C2
C2a
C3
C4
C4a
C5
C5a
C6
C7
C8
C8a
C9
C9a
C10
Vc
72.8
199.0
43.8
49.3
38.3 24.3 27.6 136.7 128.6
35.6 27.6 28.5 143.8 126.0
-
-
-
127.3 126.2 128.2 138.6
133.1 126.4 127.4 132.4
133.2 126.9 128.1 133.4
-
-
-
-
-
-
140.3
139.9
135.8
VId
VIIe
VIIIf
187.7 135.4 136.5 27.1 28.8 143.1 128.1
80.1 143.1 125.0 29.5 28.4
–
35.0 140.4 130.0 127.5 126.6
-
126.2 141.7 137.4
a
b
c
CN = 118.8 ppm; J(C40, F) = 249.9 Hz, J(C30, F) = 21.5 Hz, J(C20, F) = 8.3 Hz, J(C10, F) = 3.6 Hz; C-20,60 = 129.2 ppm,
d
e
C-30,50 = 128.3 ppm, C-40 = 125.9 ppm;
C-30,50 = 128.4 ppm, C-40 = 128.5 ppm; C-20,60 = 128.7 ppm, C-30,50 = 128.0 ppm, C-40 = 126.4 ppm
C-20,60 = 129.1 ppm, C-30,50 = 128.3 ppm, C-40 = 128.6 ppm;
C-20,60 = 129.8 ppm,
f
Fig. 2 Asymmetric units of
IIIa–IIId with thermal
ellipsoids at 50% probability
level
40 (Fig. 1) do not show clear lengthening/shortening effects
on the C3–C3a or C3a–C10 bond distances (Table 4),
which seem to vary independently in the range of
The substituents of two independent molecules in IIIa and
IIId have also similar spatial orientation.
Crystal structure of V is a racemic mixture in triclinic
space group P-1. Molecule V has chiral centers at C1 and
˚
1.31–1.38 A for the former and 1.44–1.48 A for the latter.
˚
123

Struct Chem (2012) 23:209–217
215
Table 4 Selected structural
parameters for IIIa–IIId
IIIaa
IIIbb
173.7(6)
IIIc
IIIda
\(C4a–C4–C3–C3a) [°]
\(C8a–O1–C2–C3) [°]
\(C20-C10-C3a-C3) [°]
\(C60–C10–C3a–C3) [°]
\(plane1–plane2)c [°]
-165.4(4)
167.7(3)
-164.5(3)
163.6(4)
-170.3(6)
176.7(6)
-168.2(6)
-49.7(8)
51.7(8)
176.8(3)
51.1(7)
-45.9(4)
-35.3(6)
145.8(4)
53.27(8)
44.1(4)
-51.3(7)
-50.0(4)
-47.0(9)
49.0(8)
34.4(11)
-26.1(11)
23.7(12)
-25.6(12)
22.6(12)
156.0(7)
-155.2(8)
157.2(7)
-155.1(7)
48.4(2)
32.7(6)
-38.6(11)
-29.4(6)
-148.5(7)
-149.4(4)
147.1(7)
156.3(4)
a
Two molecules in asymmetric
unit
b
58.8(2)
60.6(2)
54.82(8)
49.72(9)
Four molecules in asymmetric
48.1(2)
unit
c
46.9(2)
Planes of aryl rings C10–C60
and C4a–C8a
50.5(2)
C2. Figure 3 shows the structure with two molecules in
asymmetric unit (1R,2R enantiomers). The other molecule
has also a disorder in the aromatic ring of the benzyl group
(major/minor orientations 0.7/0.3). There were two possi-
ble positions found for hydroxyl group proton for both
crystallographically independent molecules from electron
density map and their population parameters were set to 0.5
in the refinement. This disorder shows that O–H proton
points either to the O atom of to the other molecule in
asymmetric unit or to the O atom of adjacent molecule on
the other side. Thus, these two molecules are connected to
each other and also to adjacent ones with O–HꢀꢀꢀO hydro-
gen bonds (Table 5) via these hydroxyl groups, forming an
infinite chain through the crystal. The adjacent pair of
asymmetric unit along this chain shows 1S,2S chirality, the
next pair is 1R,2R again and so on. Additionally, one
C–Hꢀꢀꢀp and one pꢀꢀꢀp contacts were found from the crystal
data (see Electronic Supplementary Material), but they are
very weak and of minor (if any) importance in structure
stabilization.
side of the plane defined by adjacent phenyl ring. In V the
benzylic substituent is in the equatorial position, while in
the two already known structures it is on axial position (O
equatorial in the latter [47]). The latter related compound
has also the similar angle between aromatic planes
[72.9(4)°] with major orientations in V, while the former
has angle value [45.9(5)°] closer to one with minor ori-
entation of disordered molecule.
Compound VI has a chiral center at C2, but the crys-
tallized structure is a racemic mixture in monoclinic space
group C2/c. Only aromatic ring and the conjugated car-
bonyl group are in the same plane. Carbon C4 is almost in
that plane, but the rest of the molecule is slightly twisted
(to the right on the chosen molecule in asymmetric unit in
Fig. 3) and it is also observed from the value of C8a–C1–
C2–C2a dihedral angle (Table 5). Small static disorder was
found to occur in the case of C3 and C2a, but the solving of
it was not successful without using strong positional and
anisotropic constraints and it was not resolved in the least
squares refinement. The angle between the planes of two
aromatic rings (Table 5) is smaller than in V but larger than
in IIIa–IIId and most of the related 3-benzylidene-4-
chromanone structures [35–44]. Three known 2-benzyl-1-
tetralone derivatives [48–50] show larger inclination angles
(74°–80°) between aromatic planes, but slightly smaller
twist of the molecule end, according to C8a–C1–C2–C2a
dihedral angles (162°–168°). One C–Hꢀꢀꢀp and one
C–HꢀꢀꢀO short intermolecular contacts were found and the
The structural search from CSD [45] showed that crystal
structure of V is the first 2-benzyl-1-tetrahydronaphthol
structure containing O–H group and –CH2– group between
the aliphatic and aromatic ring. Two closely related
molecules 2-[(dimethylamino)(phenyl)methyl]-1-methyl-
1-tetrahydronaphthol [46] and 1-methyl-30-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,20-oxiran]-1-ol [47] show
similar aliphatic ring conformations as V in crystal state, in
which the OH and carbon at position 3 are on the different
˚
former shows HꢀꢀꢀCAr distances of 2.81–2.83 A between
123

216
Struct Chem (2012) 23:209–217
hydrogen and two carbons of aryl ring. The weak C–HꢀꢀꢀO
˚
hydrogen bond has values of 3.378(5) A for CꢀꢀꢀO distance
and 139° for C–HꢀꢀꢀO angle (see Electronic Supplementary
Material). The similar C–HꢀꢀꢀO interactions can be found
from the crystals of three related 2-benzyl1-tetralones [48–
50], but the C–Hꢀꢀꢀp is very weak or does not exist at all in
those structures.
Crystal structure determined at 173 K for VII were
found to be equal to the known one previously determined
at room temperature [51]. Therefore, the structure of it is
not much discussed here, but just for comparison to com-
pounds V and VI the C8a–C1–C2–C2a dihedral angle has
the value (Table 5) closest to planar geometry and corre-
sponding well to the values of C4a–C4–C3–C3a dihedral
angle in IIIa–IIId (Table 4), which is of course expected
with the presence of carbonyl and double bond conjugated
to it. Also, the spatial orientation of the ending phenyl
group is closer to the ones found from the (E)-3-benzyli-
dene-4-chromanones than ones from more hydrogenated
derivatives V and VI, and the modeled value for C20–C10–
C2a–C2 dihedral angle [15] is about 20° larger than
observed here (Table 5). The overall shapes of the mole-
cules IIIa–IIId and VII is more planar than the shapes in
V and VI. The intermolecular interactions in VII were
previously described to be normal van der Waals interac-
tions [51]. As an update, we found three C–HꢀꢀꢀO type short
contacts in this study (see Electronic Supplementary
Material). However, the importance of the found short
interactions in structure stabilization in all crystal struc-
tures of present study (except O–HꢀꢀꢀO in V) is fairly
unknown and most probably several non-specific disper-
sive interactions play a certain role between the molecules.
Fig. 3 Asymmetric units of V–VII with thermal ellipsoids at 50%
probability level
Table 5 Selected structural
parameters for V, VI, and VII
Va
-51.4(4)
VI
-42.6(7)
VII
53.8(3)
\(C4a–C4–C3–C2) [°]
\(C8a–C1–C2–C2a) [°]
\(C20–C10–C2a–C2) [°]
-49.5(4)
-166.6(3)
-158.3(4)
-86.4(6)
97.6(5)
-171.0(2)
32.1(4)
-169.6(3)
-100.1(8) [- 88.8(17)]b
-99.3(5)
74.8(6) [101.4(7)]b
80.1(5)
a
Two molecules in asymmetric
\(C60–C10–C2a–C2) [°]
-152.0(2)
52.20(9)
unit
b
Values from the second
moiety of the disordered ring
\(plane1–plane2)c [°]
77.7(3) [56.1(5)]b
64.8(2)
c
Planes of aryl rings C10–C60
and C4a–C8a
77.08(11)
˚
d/\(O1–H1BꢀꢀꢀO21) [A/°]
2.656(4)/156(8)
2.724(5)/160(8)
2.656(4)/179(9)
2.680(5)/171(10)
d
d
˚
Symmetry operation: -x ? 1,
-y ? 1, -z ? 1
d/\(O1–H1ꢀꢀꢀO1) [A/°]
˚
d/\(O21–H21ꢀꢀꢀO1) [A/°]
d/\(O21–H21BꢀꢀꢀO21) [A/°]
e
Symmetry operation: -x,
-y ? 1, -z ? 1
e
˚
123

Struct Chem (2012) 23:209–217
217
´
16. Dimmock JR, Zello GA, Oloo EO, Quail JW, Kraatz H-B, Perjesi
Conclusions
P, Aradi F, Takacs-Novak K, Allen TM, Santos CL, Balzarini J,
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17. Levai A, Schag JB (1979) Pharmazie 34:749
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1
Complete H and 13C NMR chemical shift assignments of
´
´
seven homoisoflavonoids and six thiohomoisoflavonoids
together with four structurally close compounds are reported
based on two-dimensional homo- and heteronuclear NMR
chemical shift correlation maps. Seven single crystal X-ray
structures are also reported. The crystallographic structures
were not found congruent with the ones previously obtained
by molecular modeling. In the molecular level the structures
in present study resemble well the previously known struc-
tures of (E)-3-benzylidene-4-chromanone derivatives, but
the crystal packing is different. We wish that these data are
useful also for other researchers working with these phar-
macologically important compounds.
´
´
´
¨
}
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