Stereocontrolled photodimerization of (E)-3-benzylidene-4-chromanones in the crystalline state: The effect of a halogen group on the chromanone moiety

Article abstract of DOI:10.1055/s-0032-1317511

A series of (E)-3-benzylidene-4-chromanone derivatives are synthesized, which are substituted with a halogen group on the chromanone moiety in order to control the molecular arrangement in the crystalline state. The stereoselective photoreactions of these compounds in the solid state are examined based on the crystal structures of the reactants and products. All the examples tested undergo photodimerization, except for (E)-3-benzylidene-6-fluorochroman-4-one. The reactants with β-structures give syn-head-to-head (syn-HH) products with high selectivity. Only (E)-6-chloro-3-(4-methylbenzylidene)-chroman-4-one adopted the α-form and gives an anti-head-to-tail (anti-HT) product. Georg Thieme Verlag KG Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317511

PAPER
▌3693
paper
Stereocontrolled Photodimerization of (E)-3-Benzylidene-4-chromanones in
the Crystalline State: The Effect of a Halogen Group on the Chromanone
Moiety
Photodimerization of Crystalline (E)-3-Benzylidene-4-chromanones
Xue-Ming Cheng, Min Chen, Zhi-Tang Huang, Qi-Yu Zheng*
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100190, P. R. of China
Fax +86(10)62554449; E-mail: zhengqy@iccas.ac.cn
Received: 24.08.2012; Accepted after revision: 07.10.2012
gated the [2+2] photocycloaddition of (E)-3-benzylidene-
Abstract: A series of (E)-3-benzylidene-4-chromanone derivatives
4-chromanones possessing a halogen substituent on the
are synthesized, which are substituted with a halogen group on the
phenyl moiety in the crystalline state.13 We found that it
was not the halogen bonds, but the electron-withdrawing
chromanone moiety in order to control the molecular arrangement
in the crystalline state. The stereoselective photoreactions of these
compounds in the solid state are examined based on the crystal properties of the halogen atoms themselves that enhanced
structures of the reactants and products. All the examples tested un-
dergo photodimerization, except for (E)-3-benzylidene-6-fluoro-
chroman-4-one. The reactants with β-structures give syn-head-to-
can undergo photodimerization, which gave syn-head-to-
head (syn-HH) products with high selectivity. Only (E)-6-chloro-3-
(4-methylbenzylidene)-chroman-4-one adopted the α-form and
the face-to-face π-π interactions, which favored the for-
mation of the β-structure. Only the resulting β-structures
head (syn-HH) products with high regio- and stereoselec-
tivity. As part of our ongoing work on the photodimeriza-
tion of (E)-3-benzylidene-4-chromanones, the useful
biological activities of which have been discussed previ-
ously,14 we herein describe the effects of halogen substit-
uents on the chromanone moiety. Initially, the reactants,
(E)-3-benzylidene-4-chromanones 1a–g, were prepared
by reaction of the corresponding 4-chromanones with an
aromatic aldehyde followed by crystallization. Next, the
stereoselective photoreactions of these compounds in the
solid state were studied based on the crystal structures of
the reactants and products.
gives an anti-head-to-tail (anti-HT) product.
Key words: photodimerization, alkenes, photochemistry, chroma-
nones, halogens
As control of the stereoselectivity during the photodimer-
ization of alkenes is a key issue in synthetic organic pho-
tochemistry,1 several strategies have been directed toward
the use of various organized media and supramolecular
environments, such as crystals, clays, zeolites, biomole-
cules, micelles, self-assembled cages and artificial hosts,
etc.1a,2 Due to the highly ordered arrangement and restrict-
ed motion of molecules in the crystal lattice, alkenes sat-
isfying topochemistry postulates may undergo highly
stereoselective reactions.3 However, it is still a challenge
to stack a pair of double bonds in the crystal lattice by de-
sign, owing to the sensitivity of the crystal structure to the
molecular structure and the conditions adopted for crystal
growth.4 Polymorphic crystalline forms are common phe-
nomena, especially for organic molecules. Fluoro,5 chlo-
ro,6 bromo,7 trifluoromethyl,8 methoxy9 and acetoxy10
groups can act as steering groups directing aromatic mol-
ecules to pack in the desired crystalline order. With the
help of these substituents the crystals of aromatic com-
pounds tend to stack in a form characterized by a short ax-
is, circa 4 Å (β-structure),11 which is very important for
the photocyclization of double bonds in the solid state.
Halogen-bonded supramolecular architectures have been
studied extensively.12 However, the application of halo-
gen bond assisted solid-state photodimerization is often
rather limited in scope and cannot be extended to a wide
range of substrates. In our previous research, we investi-
Figure 1 The structures of substituted (E)-3-benzylidene-4-chroma-
nones 1a–g and the arrangements of the closest neighbors in the crys-
tal structures (ellipsoid representations) of 1a, 1d and 1f
We obtained crystalline reactants 1a–g from a mixture of
light petroleum ether, ethyl acetate, and methanol. The
single crystal structures of chromanones 1a, 1d and 1f
were determined by X-ray diffraction. For the photodi-
merization, powdered crystals of 1a–g were placed be-
SYNTHESIS 2012, 44, 3693–3698
Advanced online publication: 25.10.2012
DOI: 10.1055/s-0032-1317511; Art ID: SS-2012-H0683-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

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X.-M. Cheng et al.
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X
R
O
O
O
X
O
hν
O
crystal state
X
R
O
R
syn-HH
2b–f
1b–f
Cl
Me
O
O
O
Cl
hν
O
crystal state
O
Me
Me
O
1g
anti-HT
2g
Cl
Scheme 1 Photodimerization of chromanones 1b–g in the crystal state
tween two quartz slides and irradiated with a 500 W high- From analysis of their single crystal structures, molecules
pressure mercury lamp using a Pyrex filter under argon at of 1d and 1f were arranged in a syn-head-to-head fashion,
room temperature.
but with a slight offset (Figure 1). Chromanone 1d adopt-
ed a typical β-structure and the distances between the dou-
ble bonds were 4.08 Å, and crucially less than the
maximum 4.2 Å. In contrast, chromanone 1f adopted a
partially distorted β-structure in which all the molecules
were arranged in a syn-head-to-head manner, but with two
sets of distances between the adjacent reactive double
bonds. The distances between the first set were 4.11 Å and
4.17 Å, and those of the second set were 3.84 Å and 3.79
Å. All these lengths are less than 4.2 Å, and we are in-
clined to the view that the photoreaction occurs between
molecules separated by the shortest distances. Halogen–
halogen interactions can be ignored in compounds 1d and
1f, because the shortest halogen–halogen distances are
greater than the sum of the van der Waals radii. Only
weak C–H···O, C–H···X and π-π interactions were found
in these crystals. Therefore, in analogy to compounds with
a halogen substituent on the phenyl moiety, (E)-3-benzyl-
idene-4-chromanones containing a halogen on the chro-
manone moiety prefer to adopt a β-structure. The face-to-
face π-stacking was attributed to the electron-withdraw-
ing nature of the halogen atoms,16 which affected the ar-
rangement of the chromanone moiety in the compounds
described herein.
A knowledge of the packing arrangements of the reagents
in the crystal state is a basic requirement for understand-
ing their topochemical reactivity. Alkenes arranged in a
parallel orientation with a center-to-center separation of
less than 4.2 Å can undergo photocycloaddition.3 Due to
the similarity in size of fluorine and hydrogen atoms, (E)-
3-benzylidene-6-fluorochroman-4-one (1a) and (E)-3-
benzylidene-4-chromanone15 are isostructural. On analyz-
ing the crystal structure of 1a (Figure 1), the closest dis-
tance between two parallel C=C bonds was found to be
5.24 Å. Therefore, chromanone 1a was unable to undergo
photodimerization in the solid state, in analogy to (E)-3-
benzylidene-4-chromanone.13 For compounds 1b–g,
clean photodimerizations occurred (Scheme 1 and Table
1).
Table 1 Photodimerization of (E)-3-Benzylidene-4-chromanones
1b–g in the Solid State
Entry Substrate Time
(h)a
Conversion Yield
Stereochemistry
(%)b
(%)c
1
2
3
4
5
6
1b
1c
1d
1e
1f
20
20
30
7
82
85
78
77
90
88
51
56
46
74
57
39
syn-HH
syn-HH
syn-HH
syn-HH
syn-HH
anti-HT
Although we did not obtain good quality single crystals of
chromanones 1b, 1c and 1e suitable for X-ray analysis,
they should adopt the same arrangement as compounds 1d
or 1f, as deduced from their similar behavior in the photo-
dimerization reactions (Table 1). The progress of the pho-
toreactions was monitored by 1H NMR spectroscopy and
thin-layer chromatography. The dimer was obtained as the
major product, which was purified by column chromatog-
raphy. By-products of this reaction were not isolated, nor
10
10
1g
a The reaction was deemed complete on reaching a photostationary
state.
b The conversion was determined by 1H NMR spectroscopy.
c Yield of isolated product.
1
observed by H NMR spectroscopy. The low yield of
products was due to deformation of the substrates during
the reaction and the lack of molecular flexibility. X-ray
Synthesis 2012, 44, 3693–3698
© Georg Thieme Verlag Stuttgart · New York

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Photodimerization of Crystalline (E)-3-Benzylidene-4-chromanones
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1
crystal structure (Figure 2) and H NMR spectroscopic In conclusion, we have synthesized a series of (E)-3-ben-
analysis indicated that the stereochemistry of dimer 2f zylidene-4-chromanone derivatives containing a halogen
was syn-head-to-head (syn-HH). The 1H NMR spectra of substituent on the chromanone moiety, the presence of
products 2b–e were similar to that of 2f, and we therefore which allows favorable face-to-face arrangement of the
deduce that they also adopt syn-head-to-head stereochem- aromatic rings in the crystalline state. The solid-state pho-
istry. The high regio- and stereoselectivity of this photo- toreactions of these compounds possessing β-structures
dimerization reaction can be attributed to the constricted were examined and showed high selectivity for the forma-
arrangement in the crystalline state.
tion of syn-head-to-head products. In addition, due to the
introduction of the halogen group, (E)-6-chloro-3-(4-
methylbenzylidene)-chroman-4-one (1g), which exists in
the α-form, can also dimerize but gives an anti-head-to-
tail product.
All reagents and solvents were used without any further purifica-
tion. Column chromatography was performed using 200–300 mesh
silica gel (Yantai, China). Petroleum ether (PE) refers to the fraction
boiling in the 60–90 °C range. Melting points were recorded on a
Laboratory Devices X-4 apparatus and are uncorrected. IR spectra
were obtained using a Nicolet 380 FT-IR spectrometer as KBr discs,
wavenumbers are reported in cm–1. NMR spectra were recorded on
a Bruker 400 spectrometer at 400 MHz (1H) and 100 MHz (13C), us-
ing CDCl3 as the solvent unless otherwise specified. Chemical
shifts (δ) are reported in ppm relative to TMS. High-resolution mass
spectra were recorded on a Micromass UK MS spectrometer. UV ir-
radiation experiments were conducted with an APX UV photoreac-
tion apparatus together with a 200 V, 500 W UV lamp (Xujiang
Electrical Factory), using a Pyrex filter (>300 nm) under an argon
atmosphere at room temperature.
Figure 2 The X-ray crystal structures (ellipsoid representations) of
dimers 2f and 2g
(E)-3-Benzylidene-4-chromanones 1a–g; General Procedure
A round-bottom flask was charged with the appropriate 4-chroma-
none derivative (3.4 mmol) and aromatic aldehyde (3.6 mmol). This
was dissolved in MeOH (20 ml) and concd hydrochloride (10 ml).
The resulting soln was heated at reflux temperature for 24 h and
then diluted with H2O. Filtration followed by crystallization from
MeOH gave the pure product. Crystals suitable for X-ray analysis
were grown from a mixture of PE–EtOAc–MeOH.
(E)-3-Benzylidene-6-fluorochroman-4-one (1a)
The title compound was prepared from 6-fluorochroman-4-one
(564 mg, 3.4 mmol) and benzaldehyde (383 mg, 3.6 mmol) accord-
ing to the general procedure.
Figure 3 1H NMR (400 MHz, CDCl3) spectra of: a) 2f and b) 2g
However, the 1H NMR spectrum of dimer 2g was differ-
ent from that of 2f (Figure 3). The X-ray crystal structure
of 2g confirmed that it was an anti-head-to-tail (anti-HT)
product (Figure 2), which may indicate that its precursor,
chromanone 1g adopted an α-structure. Although we
failed to obtain single crystals of 1g suitable for X-ray
analysis, the X-ray structure of (E)-3-(4-methylbenzyli-
Yield: 579 mg (67%); yellow solid.
1H NMR (400 MHz, CDCl3): δ = 7.89 (s, 1 H), 7.67 (dd, J = 3.2, 8.4
Hz, 1 H), 7.48–7.42 (m, 3 H), 7.32 (d, J = 1.2 Hz, 1 H), 7.30 (s, 1
H), 7.23–7.18 (m, 1 H), 6.95 (dd, J = 4.0, 8.8 Hz, 1 H), 5.34 (d, J =
1.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 181.75, 159.03, 157.55, 156.63,
138.40, 134.43, 130.49, 130.22, 129.87, 129.00, 123.68, 123.43,
dene)-4-chromanone13 could provide some clues in rela- 122.84, 119.83, 119.76, 113.21, 112.97, 67.95.
The spectroscopic data are in accordance with those reported.17
tion to the solid-state arrangement. Steric hindrance
between the methyl groups results in them orienting away
from each other leading to the formation of an α-structure.
The two adjacent C=C bonds in (E)-3-(4-methylbenzyli-
dene)-4-chromanone are separated by distances of 4.00 Å
and 4.10 Å, but they are not parallel. Therefore, this sub-
strate cannot dimerize when subjected to irradiation. In
the case of 1g, the halogen substituent on the chromanone
moiety increased the face-to-face π-π interactions be-
tween the aromatic rings. The distances between the two
adjacent C=C bonds in 1g are thus shorter than those of
(E)-3-(4-methylbenzylidene)-4-chromanone and its pho-
todimerization occurs easily.
(E)-3-Benzylidene-6-chlorochroman-4-one (1b)
The title compound was prepared from 6-chlorochroman-4-one
(619 mg, 3.4 mmol) and benzaldehyde (383 mg, 3.6 mmol) accord-
ing to the general procedure.
Yield: 652 mg (71%); white solid.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 2.4 Hz, 1 H), 7.89 (s,
1 H), 7.48–7.41 (m, 4 H), 7.32 (d, J = 1.2 Hz, 1 H), 7.30 (s, 1 H),
6.93 (d, J = 8.8 Hz, 1 H), 5.35 (d, J = 1.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 181.39, 159.76, 138.56, 135.89,
134.37, 130.25, 129.92, 129.01, 127.61, 127.43, 123.01, 119.87,
67.95.
The spectroscopic data are in accordance with those reported.17
© Georg Thieme Verlag Stuttgart · New York
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(E)-3-Benzylidene-6-bromochroman-4-one (1c)
The title compound was prepared from 6-bromochroman-4-one
(768 mg, 3.4 mmol) and benzaldehyde (383 mg, 3.6 mmol) accord-
ing to the general procedure.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 2.4 Hz, 1 H), 7.87 (s,
1 H), 7.42 (dd, J = 2.4, 8.8 Hz, 2 H), 7.28–7.20 (m, 3 H), 6.93 (d,
J = 8.8 Hz, 1 H), 5.36 (s, 2 H), 2.41 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 181.42, 159.70, 140.48, 138.67,
135.78, 131.58, 130.43, 129.77, 129.44, 127.55, 127.42, 123.07,
119.83, 68.07, 21.71.
Yield: 737 mg (69% yield); white solid.
1H NMR (400 MHz, CDCl3): δ = 8.13 (d, J = 2.4 Hz, 1 H), 7.89 (s,
1 H), 7.56 (dd, J = 2.4, 8.8 Hz, 1 H), 7.49–7.42 (m, 3 H), 7.32 (d,
J = 1.2 Hz, 1 H), 7.30 (s, 1 H), 6.88 (d, J = 8.8 Hz, 1 H), 5.35 (d, J =
1.6 Hz, 2 H).
The spectroscopic data are in accordance with those reported.20
Photodimerization; General Procedure
Powdered 3-benzylidene-4-chromanone derivative 1b–g sand-
wiched between two quartz plates and placed in a Pyrex tube was
irradiated with a 500 W high-pressure mercury lamp under Ar. The
crude photolysate was subjected to silica gel column chromatogra-
phy (PE–CH2Cl2, 1:2). Solid dimers were recrystallized from a mix-
ture of PE–EtOAc.
13C NMR (100 MHz, CDCl3): δ = 181.28, 160.22, 138.68, 138.61,
134.37, 130.57, 130.26, 129.94, 129.02, 123.50, 120.23, 114.79,
67.94.
The spectroscopic data are in accordance with those reported.18
(E)-3-Benzylidene-6-iodochroman-4-one (1d)
The title compound was prepared from 6-iodochroman-4-one (932
mg, 3.4 mmol) and benzaldehyde (383 mg, 3.6 mmol) according to
the general procedure.
syn-HH Dimer 2b
The product was obtained from chromanone 1b (200 mg).
Yield: 102 mg (51%); white solid; mp 234–235 °C.
Yield: 739 mg (60%); white solid.
IR (KBr): 1693, 1604, 1477, 1420, 1280, 1201, 704 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.31 (d, J = 1.6 Hz, 1 H), 7.88 (s,
1 H), 7.73 (dd, J = 2.0, 8.4 Hz, 1 H), 7.47–7.42 (m, 3 H), 7.31 (d,
J = 7.2 Hz, 2 H), 6.75 (d, J = 8.4 Hz, 1 H), 5.35 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 181.07, 160.87, 144.31, 138.55,
136.72, 134.34, 130.24, 130.15, 129.92, 129.00, 123.98, 120.53,
84.46, 67.89.
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 2.4 Hz, 2 H), 7.24–
7.18 (m, 8 H), 7.01–6.99 (m, 4 H), 6.51 (d, J = 8.8 Hz, 2 H), 5.22 (s,
2 H), 4.79 (d, J =13.2 Hz, 2 H), 4.50 (d, J = 13.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 189.49, 159.55, 136.06, 135.14,
129.77, 128.39, 126.91, 126.69, 120.48, 118.65, 68.91, 54.12,
39.63.
The spectroscopic data are in accordance with those reported.18
HRMS (EI): m/z [M]+ calcd for C32H22O4Cl2: 540.0895; found:
540.0890.
(E)-6-Chloro-3-(4-fluorobenzylidene)chroman-4-one (1e)
The title compound was prepared from 6-chlorochroman-4-one
(619 mg, 3.4 mmol) and 4-fluorobenzaldehyde (446 mg, 3.6 mmol)
according to the general procedure.
syn-HH Dimer 2c
The product was obtained from chromanone 1c (200 mg).
Yield: 112 mg (56%); white solid; mp 226–228 °C.
IR (KBr): 1692, 1600, 1474, 1416, 1280, 1201, 705 cm–1.
Yield: 392 mg (40%); white solid; mp 167–168 °C.
IR (KBr): 1672, 1603, 1587, 1508, 1475, 1424, 1288, 1222, 1160,
819 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 2.4 Hz, 1 H), 7.84 (s,
1 H), 7.43 (dd, J = 2.4, 8.8 Hz, 1 H), 7.32–7.28 (m, 2 H), 7.15 (t, J =
8.4 Hz, 2 H), 6.93 (d, J = 8.8 Hz, 1 H), 5.32 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 181.21, 164.80, 162.30, 159.69,
137.28, 135.96, 132.32, 132.23, 130.55, 130.11, 127.70, 127.44,
122.94, 119.88, 116.39, 116.17, 67.82.
1H NMR (400 MHz, CDCl3): δ = 7.62 (d, J = 2.4 Hz, 2 H), 7.33 (dd,
J = 2.4, 8.4 Hz, 2 H), 7.24–7.23 (m, 6 H), 7.01–6.99 (m, 4 H), 6.44
(d, J = 8.4 Hz, 2 H), 5.22 (s, 2 H), 4.79 (d, J = 13.2 Hz, 2 H), 4.49
(d, J = 13.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 189.36, 159.95, 138.84, 135.13,
129.83, 129.78, 128.40, 126.93, 121.02, 118.96, 113.97, 68.85,
54.09, 39.61.
HRMS (EI): m/z [M]+ calcd for C32H22O479Br2: 627.9885; found:
627.9871; m/z [M]+ calcd for C32H22O479Br81Br: 629.9864; found:
629.9881; m/z [M]+ calcd for C32H22O481Br2: 631.9844; found:
631.9852.
HRMS (EI): m/z [M]+ calcd for C16H10O2FCl: 288.0353; found:
288.0357.
(E)-6-Chloro-3-(4-chlorobenzylidene)chroman-4-one (1f)
The title compound was prepared from 6-chlorochroman-4-one
(619 mg, 3.4 mmol) and 4-chlorobenzaldehyde (504 mg, 3.6 mmol)
according to the general procedure.
syn-HH Dimer 2d
The product was obtained from chromanone 1d (200 mg).
Yield: 92 mg (46%); white solid; mp 247–249 °C.
IR (KBr): 1692, 1594, 1473, 1411, 1282, 1199, 731, 705 cm–1.
Yield: 434 mg (42%); white solid.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 2.4 Hz, 1 H), 7.82 (s,
1 H), 7.45–7.42 (m, 3 H), 7.25 (s, 1 H), 7.23 (s, 1 H), 6.94 (d, J =
8.8 Hz, 1 H), 5.31 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 181.11, 159.74, 137.06, 136.10,
136.03, 132.79, 131.45, 130.78, 129.36, 127.76, 127.46, 122.91,
119.90, 67.80.
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 2.0 Hz, 2 H), 7.50 (dd,
J = 8.0, 2.0 Hz, 2 H), 7.25–7.23 (m, 6 H), 7.00 (t, J = 6.4 Hz, 4 H),
6.31 (d, J = 8.4 Hz, 2 H), 5.21 (s, 2 H), 4.78 (d, J = 13.6 Hz, 2 H),
4.48 (d, J = 13.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 189.21, 160.54, 144.43, 136.01,
135.12, 129.77, 128.39, 126.91, 121.58, 119.24, 83.44, 68.70,
53.97, 39.51.
The spectroscopic data are in accordance with those reported.19
(E)-6-Chloro-3-(4-methylbenzylidene)chroman-4-one (1g)
The title compound was prepared from 6-chlorochroman-4-one
(619 mg, 3.4 mmol) and 4-methylbenzaldehyde (432 mg, 3.6 mmol)
according to the general procedure.
HRMS (EI): m/z [M]+ calcd for C34H22O4I2: 723.9608; found:
723.9616.
syn-HH Dimer 2e
The product was obtained from chromanone 1e (200 mg).
Yield: 493 mg (51%); white solid.
Yield: 148 mg (74%); white solid; mp 281–283 °C.
IR (KBr): 1689, 1652, 1603, 1558, 1508, 1477, 1418, 1282 cm–1.
Synthesis 2012, 44, 3693–3698
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Photodimerization of Crystalline (E)-3-Benzylidene-4-chromanones
3697
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 2.0 Hz, 2 H), 7.21 (dd,
J = 8.8, 2.4 Hz, 2 H), 6.95 (d, J = 6.8 Hz, 8 H), 6.53 (d, J = 8.4 Hz,
2 H), 5.17 (s, 2 H), 4.76 (d, J = 13.2 Hz, 2 H), 4.48 (d, J = 13.2 Hz,
2 H).
13C NMR (100 MHz, CDCl3): δ = 189.29, 163.03, 160.57, 159.47,
136.21, 131.32, 131.24, 130.55, 127.08, 126.70, 120.42, 118.70,
115.64, 115.43, 68.79, 54.02, 39.13.
2680.58(8) Å3, Z = 4, Dcalcd = 1.512 g cm–3 (MoKα, λ = 0.71073 Å),
T = 173(2) K, R1 = 0.0714, wR2 = 0.1247.
anti-HT Dimer 2g (CCDC 895348): C34H26Cl2O4, M = 569.45, or-
thorhombic, space group Pna2(1), a = 14.7893(13) Å, b = 8.819(2)
Å, c = 20.761(3) Å, α = 90.00°, β = 90.00°, γ = 90.00°, V = 2707.7(8)
Å3, Z = 4, Dcalcd = 1.397 g cm–3 (MoKα, λ = 0.71073 Å), T = 173(2)
K, R1 = 0.0500, wR2 = 0.1062.
HRMS (EI): m/z [M]+ calcd for C32H20O4F2Cl2: 576.0707; found:
576.0714.
Acknowledgment
syn-HH Dimer 2f
Financial support from the Major State Basic Research Develop-
ment Program of China (2011CB932501), the National Natural Sci-
ence Foundation of China (20932004), and the Chinese Academy of
Sciences is gratefully acknowledged.
The product was obtained from chromanone 1f (200 mg).
Yield: 114 mg (57%); white solid; mp 291–292 °C.
IR (KBr): 1686, 1604, 1476, 1418, 1278 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.47 (d, J = 2.4 Hz, 2 H), 7.24–
7.19 (m, 6 H), 6.91 (d, J = 8.4 Hz, 4 H), 6.52 (d, J = 8.8 Hz, 2 H),
5.15 (s, 2 H), 4.73 (d, J = 13.2 Hz, 2 H), 4.45 (d, J = 13.2 Hz, 2 H).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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13C NMR (100 MHz, CDCl3): δ = 189.16, 159.45, 136.27, 133.32,
133.18, 130.98, 128.76, 127.10, 126.68, 120.33, 118.72, 68.67,
54.00, 39.17.
References
HRMS (EI): m/z [M]+ calcd for C32H20O435Cl4: 608.0116; found:
608.0106; m/z [M]+ calcd for C32H20O435Cl337Cl: 610.0086; found:
610.0078; m/z [M]+ calcd for C32H20O435Cl237Cl2: 612.0057; found:
612.0063.
(1) (a) MacGillivray, L. R. J. Org. Chem. 2008, 73, 3311.
(b) Nagarathinam, M.; Peedikakkal, A. M. P.; Vittal, J. J.
Chem. Commun. 2008, 5277.
(2) (a) Koshima, H.; Ding, K.; Chisaka, Y.; Matsuura, T. J. Am.
Chem. Soc. 1996, 118, 12059. (b) Koshima, H.; Nakagawa,
T.; Matsuura, T. Tetrahedron Lett. 1997, 38, 6063.
(c) Koshima, H.; Ding, K.; Chisaka, Y.; Matsuura, T.;
Miyahara, I.; Hirotsu, K. J. Am. Chem. Soc. 1997, 119,
10317. (d) Coates, G. W.; Dunn, A. R.; Henling, L. M.;
Ziller, J. W.; Lobkovsky, E. B.; Grubbs, R. H. J. Am. Chem.
Soc. 1998, 120, 3641. (e) Ito, Y.; Hosomi, H.; Ohba, S.
Tetrahedron 2000, 56, 6833. (f) MacGillivray, L. R.; Reid,
J. L.; Ripmeester, J. A. J. Am. Chem. Soc. 2000, 122, 7817.
(g) Amirsakis, D. G.; Garcia-Garibay, M. A.; Rowan, S. J.;
Stoddart, J. F.; White, A. J. P.; Williams, D. J. Angew. Chem.
Int. Ed. 2001, 40, 4256. (h) Friscic, T.; MacGillivray, L. R.
Chem. Commun. 2003, 1306. (i) Ouyang, X.; Fowler, F. W.;
Lauher, J. W. J. Am. Chem. Soc. 2003, 125, 12400. (j) Gao,
X.; Friscic, T.; MacGillivray, L. R. Angew. Chem. Int. Ed.
2004, 43, 232. (k) Caronna, T.; Liantonio, R.; Logothetis, T.
A.; Metrangolo, P.; Pilati, T.; Resnati, G. J. Am. Chem. Soc.
2004, 126, 4500. (l) Varshney, D. B.; Gao, X.; Friscic, T.;
MacGillivray, L. R. Angew. Chem. Int. Ed. 2006, 45, 646.
(m) Yang, J.; Dewal, M. B.; Shimizu, L. S. J. Am. Chem.
Soc. 2006, 128, 8122. (n) Hill, Y.; Briceno, A. Chem.
Commun. 2007, 3930. (o) Yang, J.; Dewal, M. B.; Profeta, S.
Jr.; Smith, M. D.; Li, Y.; Shimizu, L. S. J. Am. Chem. Soc.
2008, 130, 612. (p) Mir, M. H.; Koh, L. L.; Tan, G. K.;
Vittal, J. J. Angew. Chem. Int. Ed. 2010, 49, 390.
anti-HT Dimer 2g
The product was obtained from chromanone 1g (200 mg).
Yield: 78 mg (39%); white solid; mp 285–287 °C.
IR (KBr): 1681, 1601, 1513, 1473, 1416, 1270, 1202, 1137, 1011,
824 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.70 (s, 2 H), 7.30 (d, J = 8.4 Hz,
2 H), 7.00 (d, J = 7.6 Hz, 4 H), 6.91 (d, J = 8.0 Hz, 4 H), 6.75 (d, J =
8.8 Hz, 2 H), 5.13 (s, 2 H), 5.10 (d, J = 12.0 Hz, 2 H), 3.92 (d, J =
11.6 Hz, 2 H), 2.20 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 193.19, 159.82, 137.53, 135.87,
131.13, 129.25, 129.20, 126.83, 121.96, 119.29, 74.00, 51.53,
46.29, 21.14.
HRMS (EI): m/z [M]+ calcd for C34H26O4Cl2: 568.1208; found:
568.1215.
Crystallographic Data
Crystallographic data have been deposited at the Cambridge Crys-
tallographic Data Centre.
(E)-3-Benzylidene-6-fluorochroman-4-one
(1a)
(CCDC
895351): C16H11FO2, M = 254.25, triclinic, space group P1, a =
7.9417(16) Å, b = 8.5071(17) Å, c = 9.1657(18) Å, α = 90.45(3)°,
β = 93.40(3)°, γ = 105.31(3)°, V = 596.0(2) Å3, Z = 2, Dcalcd = 1.417
g cm–3 (MoKα, λ = 0.71073 Å), T = 173(2) K, R1 = 0.0507, wR2 =
0.1201.
(q) Sokolov, A. N.; Bucar, D.-K.; Baltrusaitis, J.; Gu, S. X.;
MacGillivray, L. R. Angew. Chem. Int. Ed. 2010, 49, 4273.
(r) Pemberton, B. C.; Barooah, N.; Srivatsava, D. K.;
Sivaguru, J. Chem. Commun. 2010, 225. (s) Grove, R. C.;
Malehorn, S. H.; Breen, M. E.; Wheeler, K. A. Chem.
Commun. 2010, 7322. (t) Bhogala, B. R.; Captain, B.;
Parthasarathy, A.; Ramamurthy, V. J. Am. Chem. Soc. 2010,
132, 13434. (u) Kole, G. K.; Tan, G. K.; Vittal, J. J. J. Org.
Chem. 2011, 76, 7860.
(E)-3-Benzylidene-6-iodochroman-4-one (1d) (CCDC 895352):
C16H11IO2, M = 362.15, monoclinic, space group P2(1)/n, a =
4.0816(8) Å, b = 28.597(6) Å, c = 11.356(2) Å, α = 90.00°, β =
98.97(3)°, γ = 90.00°, V = 1309.3(5) Å3, Z = 4, Dcalcd = 1.837 g cm–3
(MoKα, λ = 0.71073 Å), T = 173(2) K, R1 = 0.0426, wR2 = 0.1238.
(E)-6-Chloro-3-(4-chlorobenzylidene)chroman-4-one
(1f)
(CCDC 895349): C16H10Cl2O2, M = 305.14, monoclinic, space
group Pc, a = 13.570(3) Å, b = 7.6900(15) Å, c = 13.205(3) Å, α =
(3) (a) Schmidt, G. M. J. Pure Appl. Chem. 1971, 27, 647.
(b) Wegner, G. Pure Appl. Chem. 1977, 49, 443.
(4) Yang, S.-Y.; Naumov, P.; Fukuzumi, S. J. Am. Chem. Soc.
2009, 131, 7247.
90.00°, β = 106.25(3)°, γ = 90.00°, V = 1322.9(5) Å3, Z = 4, Dcalcd
=
1.532 g cm–3 (MoKα, λ = 0.71073 Å), T = 173(2) K, R1 = 0.0368,
wR2 = 0.0869.
syn-HH Dimer 2f (CCDC 895350): C32H20Cl4O4, M = 610.31,
monoclinic, space group P2(1)/n, a = 14.091(3) Å, b = 8.1533(16)
Å, c = 23.492(3) Å, α = 90.00°, β = 96.69(3)°, γ = 90.00°, V =
(5) (a) Kumar, V. A.; Begum, N. S.; Venkatesan, K. J. Chem.
Soc., Perkin Trans. 2 1993, 463. (b) Vishnumurthy, K.;
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3693–3698

3698
X.-M. Cheng et al.
PAPER
Ellis, G. P., Ed.; John Wiley & Sons: New York, 1977.
Row, T. N. G.; Venkatesan, K. Photochem. Photobiol. Sci.
2002, 1, 427.
(b) Al Nakib, T.; Bezjak, V.; Meegan, M. J.; Chandy, R. Eur.
J. Med. Chem. 1990, 25, 455. (c) Kirkiacharian, B. S.;
Gomis, M.; Koutsourakis, P. Eur. J. Med. Chem. 1989, 24,
309. (d) Wall, M. E.; Wani, M. C.; Manikumar, G.; Taylor,
H.; McGivney, R. J. Nat. Prod. 1989, 52, 774. (e) Desideri,
N.; Olivieri, S.; Stein, M. L.; Sgro, R.; Orsi, N.; Conti, C.
Antiviral Chem. Chemother. 1997, 8, 545. (f) Desideri, N.;
Bolasco, A.; Rossella, F.; Monaco, L. P.; Orallo, F.; Yanez,
M.; Ortuso, F.; Alcaro, S. J. Med. Chem. 2011, 54, 2155.
(15) Katrusiak, A.; Ratajczak-Sitarz, M.; Kaluski, Z.; Orlov, V.
D. Acta Cryst. 1987, C43, 103.
(6) Elgavi, A.; Green, B. S.; Schmidt, G. M. J. J. Am. Chem. Soc.
1973, 95, 2058.
(7) Venugopalan, P.; Bharati Rao, T.; Venkatesan, K. J. Chem.
Soc., Perkin Trans. 2 1991, 981.
(8) (a) Liu, J.; Boarman, K. J. Chem. Commun. 2005, 340.
(b) Liu, J.; Wendt, N. L.; Boarman, K. J. Org. Lett. 2005, 7,
1007.
(9) Gnanaguru, K.; Ramasubbu, N.; Venkatesan, K.;
Ramamurthy, V. J. Org. Chem. 1985, 50, 2337.
(10) Ramamurthy, V.; Venkatesan, K. Chem. Rev. 1987, 87, 433.
(11) Sarma, J. A. R. P.; Desiraj, G. R. Acc. Chem. Res. 1986, 19,
222.
(16) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990,
112, 5525.
(12) Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Acc.
Chem. Res. 2005, 38, 386.
(17) Biju, A. T.; Wurz, E. N.; Glorius, F. J. Am. Chem. Soc. 2010,
132, 5970.
(13) Cheng, X.-M.; Huang, Z.-T.; Zheng, Q.-Y. Tetrahedron
2011, 67, 9093.
(14) (a) Lockhart, I. M. The Chemistry of Heterocyclic
Compounds, Chromenes, Chromanones and Chromones;
(18) Kumar, S.; Makrandi, K. J. E–J. Chem. 2012, 1251.
(19) Conti, C.; Desideri, N. Bioorg. Med. Chem. 2011, 19, 3720.
(20) Mandal, T.; Pal, R.; Mondal, R.; Mollic, A. E–J. Chem.
2011, 863.
Synthesis 2012, 44, 3693–3698
© Georg Thieme Verlag Stuttgart · New York