Photochemical generation of cyclophanes from 1,3,5-trisubstituted benzenes with chalcone chromophores

Article abstract of DOI:10.1002/ejoc.200700010

(E,E,E)-1,3,5-Tricinnamoylbenzene (7a) photodimerizes in solution to the [4.4.4](1,3,5)cyclophane 8a. The process consists of three consecutive steps in which cisoid enone conformations of 7a react in regio- and stereoselective anti-head-to-head cycloaddi

Full text of DOI:10.1002/ejoc.200700010

FULL PAPER
DOI: 10.1002/ejoc.200700010
Photochemical Generation of Cyclophanes from 1,3,5-Trisubstituted Benzenes
with Chalcone Chromophores
Elena Karpuk,[a] Dieter Schollmeyer,[a] and Herbert Meier*[a]
Keywords: Cycloaddition / Cyclophanes / Diastereoselectivity / Photochemistry / Regioselectivity
(E,E,E)-1,3,5-Tricinnamoylbenzene (7a) photodimerizes in
solution to the [4.4.4](1,3,5)cyclophane 8a. The process con-
cycloadditions. Photolyses in the crystalline state yield di-
mers by topochemically controlled syn-head-to-tail processes
sists of three consecutive steps in which cisoid enone confor- (7a Ǟ 10a, 13a Ǟ 15a). An efficient dimerization of 13a takes
mations of 7a react in regio- and stereoselective anti-head-
to-head cycloadditions. (E,E,E)-1,3,5-Tris(3-oxo-3-phenylpro-
place, although the distance between the olefin centers ex-
ceeds with 5.07 Å by far the limit postulated in Schmidt’s
penyl)benzene (13a), an isomer of 7 with reversed enone rule.
units, shows a single [2π+2π] cycloaddition of the same type.
Due to steric reasons, it is afterwards not capable of intramo-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
lecular processes and oligomerizes by intermolecular photo- Germany, 2007)
Introduction
Since the synthesis of [2.2](1,4)cyclophane by Brown and
Farthing[1] in 1949 and the pioneering work of Cram[2] in
the early 1950s, cyclophanes represent a highly attractive
class of compounds.[3] Many different synthetic routes were
developed for this purpose. More than 30 years ago, we
described the first applications of photocycloaddition reac-
tions for the generation of cyclophanes.[4,5] In the meantime,
various polyfunctional compounds with vinyl, styryl, cinna-
moyl or other groups, suitable for [2π+2π] cycloadditions,
were used.[3,6] Scheme 1 shows such inter- and intramolecu-
lar photocycloaddition reactions with R = H, C6H5, COOR
and n = 2, 3, 4. For X = nil, [2n]cyclophanes are formed (1
Ǟ 2), while [4n] and higher systems require X = O, CO,
etc.[3] Phanes having “decks” other than benzene, can be
prepared in the same way.
A special aspect of these photoreactions is due to the
fact that normally only (E)-configurations react,[7] but they
can react in different conformations to different stereoiso-
mers. Conformational selectivities are very rare in organic
reactions. Whereas the regiochemistry of the cycloaddition
3 Ǟ 4 is normally fixed by the molecular architecture of 3,
cyclodimerizations of 1 can follow a head-to-head or a
head-to-tail arrangement.
Scheme 1. Inter- and intramolecular [2π+2π] photocycloaddition
reactions for the formation of cyclophanes.
in the sense of threefold [2π+2π] photocycloaddition reac-
tions should result in (1,3,5)cyclophanes with 4 or 5 carbon
atoms in the three bridges – depending on head-to-head or
head-to-tail additions.
Results and Discussion
1,3,5-Tricinnamoylbenzenes 7a–d are easily accessible by
alkaline condensation reactions of 1,3,5-triacetylbenzene
(5) and benzaldehydes 6a–d (Scheme 2). The parent com-
pound 7a was obtained in a yield of 70%.[10,11] Electron-
donating substituents in the benzaldehyde components 6 re-
duce the electrophilicity of the carbonyl carbon atom and
consequently decrease the yield (18% for 7c and 30% for
7d). A detailed study of the condensation was performed
for 5 and 6b. The ratio 5/6b of 1:5 led in aqueous ethanolic
NaOH at 40 °C after 5 h to a mixture of mono- (25%), di-
(20%) and tricondensation product (7b, 3%).
We started now to study the cyclophane formation of
benzene derivatives which have in 1,3,5-position cinnamoyl
groups (chalcone substructures with X = CO and R =
C6H5).[8,9] Different regio- and stereoselective dimerizations
[a] Institut für Organische Chemie der Johannes Gutenberg-Uni-
versität,
Duesbergweg 10–14, 55099 Mainz, Germany
Fax: +49-6131-3925396
E-mail: hmeier@mail.uni-mainz.de
Eur. J. Org. Chem. 2007, 1983–1990
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1983

E. Karpuk, D. Schollmeyer, H. Meier
FULL PAPER
formations in the ground state, but certainly contains only
trans-configured double bonds. The structures 8aa, 8ab and
8ac represent [4.4.4](1,3,5)cyclophanes which can be gener-
ated in threefold head-to-head syn or anti photocycload-
ditions: 8aa from 7aЈ + 7aЈ with cis arrangement of the
heads (and tails); 8ab from 7a + 7a with trans arrangement
of the heads; 8ac from 7a + 7a with cis arrangement of the
heads.
The structures 8ad and 8ae represent [5.5.5](1,3,5)cy-
clophanes which can be generated in threefold head-to-tail
photocycloadditions: 8ad from 7aЈ + 7aЈ with cis arrange-
ment of the heads; 8ae from a mixed addition 7a + 7aЈ with
cis arrangement of the heads.
All other thinkable arrangements are too strained to per-
mit three consecutive [2π+2π] processes. Nevertheless, the
differentiation between the five isomers 8aa–8ae turned out
to be very difficult.
Scheme 2. Preparation of all-(E)-1,3,5-tricinnamoylbenzenes 7a–d.
The four-membered ring protons in 8aa, 8ab and 8ac
1
should give rise to AAЈBBЈ spin patterns in the H NMR
Purification of the reaction products by column
chromatography/crystallization yields the all-(E) configura-
tions of 7a–d. The three enone units can have cisoid or
transoid conformations. Scheme 3 demonstrates the equilib-
rium between the all-cisoid form 7a and the all-transoid
form 7aЈ. According to NOE measurements, cisoid confor-
mations are preferred. The conformational selectivity, men-
tioned before for the photocyclodimerization reactions, is a
decisive point for the cyclophane formation.
spectra; 8ad should give an A2B2 spin pattern and 8ae an
ABC2 system which is converted by molecular dynamics,
which is fast in terms of the NMR time scale, to an A2B2
system. The observed spin pattern is not in accordance with
A2B2 or ABC2 systems. Therefore, the head-to-tail adducts
8ad and 8ae can be ruled out. Calculation of the observed
AAЈBBЈ spin pattern[13] rendered the parameters listed in
Table 1 for 8a. NOE measurements showed a positive effect
for the neighborhood of the protons on the central benzene
ring (δ = 7.81 ppm) and the α-protons of the four-mem-
bered rings (δ = 3.90 ppm), but not for the β-protons (δ =
4.47 ppm). Consequently, structure 8aa can be eliminated.
The final differentiation between 8ab and 8ac proved to be
very complex since neither through-bond connectivity (H,H
coupling)[14] nor through-space connectivity (NOE) allowed
a clear decision. Ultimately, we succeeded with a mixed cy-
cloadduct. Irradiation of 7a/7b (ratio 2:1) yielded traces of
8a, the dimer 8b as a byproduct and the mixed cycloadduct
9 (Scheme 4) as major component. The statistical ratio 8a/
8b/9 would be 4:1:4; the experimental ratio was Յ4:19:77
which proves the higher reactivity of 7b compared to 7a.
The four-membered ring protons of the mixed adduct 9
have an ABCD spin pattern, and NOE measurements
Scheme 3. all-cisoid and all-transoid conformation of (E,E,E)-1,3,5-
tris(3-phenylpropenoyl)benzene (7a/7aЈ).
Upon irradiation (λՆ290 nm) in solution (2.9ϫ10–2

in CD2Cl2, λmax = 326 nm,[12] εmax = 69040 cm mmol–1) the showed that the C3 structure of 9, which corresponds to the
parent compound (E,E,E)-7a reaches soon a photostation- D3 structure 8ab is correct. Irradiation of the singlet of the
ary state. The ratio (E,E,E)/(E,E,Z)/(E,Z,Z)/(Z,Z,Z), deter- protons on the trimethoxybenzene ring (δ = 6.63 ppm) re-
1
mined by H NMR spectroscopy, amounts to 2:4:8:5. Pro- sulted in positive NOEs for both β-protons on the four-
tonation of the isomeric mixture catalyzes the reverse reac- membered rings (δ = 4.37, 4.49 ppm); that means the ter-
tion to all-(E)-7a so that (Z) conformations are below the minal benzene rings must have the trans arrangement pres-
1
detection limit of about 3% in the H NMR spectrum.
ent in 8ab and formula 8ac can be rejected. Irradiation of
Irradiation of 7a in more concentrated solutions the pure monomers 7b–d yields [4.4.4](1,3,5)cyclophanes
(14ϫ10–2  in CH2Cl2) yields 81% of a dimer 8a which whose structures correspond to 8ab.[15]
contains three four-membered rings in an arrangement with
The photochemical cyclophane formation 7 Ǟ 8 can be
a C3 axis. The process is highly selective since no other di- summarized as follows: cisoid (E) configurations of 7 react
mers can be found. The remaining 19% are monomer and in three consecutive steps in a regioselective head-to-head
small amounts of polymer.
Scheme 4 shows the five possible structures for 8a. The on the four-membered rings have always trans arrangement.
photodimerization occurs probably via an excimer whose Irradiation of 7a in the crystalline state yields a dimer
geometry may be independent of the preferred cisoid con- 10a which contains only one four-membered ring
mode, and in a stereoselective way, so that vicinal protons
1984
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Eur. J. Org. Chem. 2007, 1983–1990

Cyclophanes from 1,3,5-Trisubstituted Benzenes
FULL PAPER
Scheme 4. Possible isomeric [4.4.4](1,3,5)- and [5.5.5](1,3,5)cyclophanes 8 obtained by threefold photocycloaddition reactions of 7a and
mixed cycloadduct 9 obtained from 7a and 7b.
Table 1. 1H NMR chemical shifts (δ values in ppm, measured in topochemically controlled photodimerization comes to an
CDCl3, TMS as internal standard) and calculated[13] coupling con-
end when the crystal lattice breaks down.
stants (absolute values in Hz) of the four-membered ring protons
which generate AAЈBBЈ spin patterns in 8a, 10a, 14a and 15a.
Compd.
Cycloadd.
type
δ (A) δ (B)[a]
[a]
J
J
J
J
(AAЈ)
(AB)
(ABЈ)
(BBЈ)
8a
h-to-h
anti
4.47
5.16
4.66
5.07
3.90
4.94
4.15
4.95
9.95
0.85
9.60
0.85
8.95
10.75
8.80
0.25
6.85
0.25
6.85
9.95
0.90
9.60
0.90
10a
14a
15a
h-to-t
syn
h-to-h
anti
h-to-t
syn
10.75
[a] The protons A with signals at lower field are on the side of the
phenyl substituents, the protons B on the carbonyl side.
(Scheme 5). The structure determination of 10a is based on
one- and two-dimensional NMR studies. Irradiation of the
signal of the aromatic protons (δ = 8.47 ppm) on the central
benzene ring leads to NOEs for the four-membered ring
protons Hα (δ = 4.94 ppm), Hβ (δ = 5.16 ppm), the olefinic
Scheme 5. Photochemistry of 3a in the crystalline state and in an
amorphous film.
The protons on the four-membered ring exhibit an
protons HαЈ (δ = 7.52 ppm), HβЈ (δ = 7.87 ppm) and the AAЈBBЈ spin pattern according to the Ci symmetry of 10a;
ortho-proton (δ 7.30 ppm) of the phenyl group comparison with the corresponding data of 8ab reveals
=
(Scheme 5). This result proves the head-to-tail regioselectiv- higher δ values for 10a, because the second aromatic “deck”
3
ity and the stereoselective syn-[2π+2π] photocycloaddition is not present in 10a. Additionally, a J (cis) coupling of
reaction. Other dimers could not be found. Apart from 6.85 Hz was found for 10a which is smaller than the 3J
66% of 10a, only monomer 7a (34%) was obtained. The (trans) couplings in 8ab (Table 1).
Eur. J. Org. Chem. 2007, 1983–1990
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1985

E. Karpuk, D. Schollmeyer, H. Meier
FULL PAPER
Figure 1 shows the reaction spectra of the irradiation of transoid orientations of the enone units should play a role
a spin-coated film of 7a. The long-wavelength absorption in this context. We expected a behavior, which is similar to
causes a broader and somewhat bathochromically shifted 1,3,5-tristyrylbenzene,[5,17–19] and should lead to
a
band (λmax = 331 nm) in the amorphous state. Monochro- [2.2.2](1,3,5)cyclophane with C3h or Cs symmetry.[20] The
matic irradiation with λ = 366 nm leads to a complete dis- irradiation of 13a (λՆ290 nm) in solution (9.7ϫ10–2  in
appearance of the band. The film becomes totally insoluble CH2Cl2, λmax = 311 nm) yielded, as discussed for 7a, a mix-
in organic solvents. The chalcone chromophores enter in ture of the four (E)/(Z) isomers, a dimer 14a and a large
this aggregated but not really ordered state photopoly- amount of oligomers. Obviously, photopolymerization and
merization and photocrosslinking reactions in which finally photocrosslinking are much more effective for 13a than for
all enone building blocks are involved.
7a. Isolation of the dimer 14a by preparative TLC and spec-
troscopic characterization led to the structure of a head-to-
head adduct in which the two heads (as well as the two
tails) have a trans arrangement (Scheme 7). Due to this ste-
reochemistry, the distance between the remaining olefinic
double bonds is too large to permit the formation of a sec-
ond (and third) four-membered ring in an intramolecular
process. However, intermolecular cycloadditions are feas-
ible and yield oligomers as major products. The different
behavior of 7 and 13 is due to the different intramolecular
mobility of the monoadducts. The carbonyl groups act in
the process 7 Ǟ 8 as a kind of “joints”, whereas in the
monoadduct 14a they are on the “wrong” side.
Figure 1. Time-resolved UV/Vis spectra (absorbance A) of the mo-
nochromatic (λ = 366 nm) irradiation of a spin-coated film of 7a.
Measurement after 0, 15, 30, 45, 60, 75, 165 and 465 s (top to
bottom). The dotted line corresponds to the spectrum measured
for a 1.03ϫ10–4  solution in CH2Cl2.
Threefold alkaline condensation of 1,3,5-benzenetricar-
baldehyde (11) and the acetophenones 12a,b leads to the
compounds 13a,b which are isomers of 7a,b, but have the
opposite direction of the enone substructures.
(Scheme 6).[16]
Scheme 7. anti-head-to-head photodimerization 13a Ǟ 14a in solu-
tion and syn-head-to-tail photodimerization 13a Ǟ 15a in the crys-
talline state.
Before we tried the photolysis of 13a in the crystalline
state, we performed a crystal structure analysis. Figure 2
shows the unit cell and the arrangement of neighboring
Scheme 6. Preparation of the (E,E,E)-1,3,5-tris(3-oxo-3-phenylpro-
penyl)benzenes 13a,b.
The intramolecular mobility of the three arms in 13 is molecules 13a in the crystal. The molecules have nearly Cs
much lower than in 7 concerning the formation of excimers symmetry and are located in parallel planes. However, the
which are capable of cyclophane formation. Neither head- olefinic double bonds are in a distance which is much larger
to-tail arrangements nor the distinction between cisoid or than 4.2 Å. According to Schmidt’s rule,[21] a topochem-
1986
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Cyclophanes from 1,3,5-Trisubstituted Benzenes
FULL PAPER
Figure 2. Top: Unit cell of 13a (inclusion of solvent molecules CHCl3). Center: Platon plot of neighboring molecules (all bond lengths
and bond angles correspond to normal values). Bottom: Olefinic part in a view which is perpendicular to the view of the Platon plot.
ically controlled [2π+2π] cycloaddition should be imposs- until X-ray studies revealed, that in solution and in the
ible. However, the experiment told us that the process is molten state anti-head-to-head cycloadditions take place,
highly effective. The syn-head-to-tail adduct 15a was ob- whereas in the crystalline state syn-head-to-tail processes
tained (Scheme 7) in a yield of 57%. We explain this result occur.[24,25]
by the fact, that the parallel planes of the two reacting
In principle, the photochemical behavior of the benzene
molecules have an ideal distance of 1.46 Å, which enables a derivatives studied here, with chalcone chromophores in
sufficient interaction of the π-orbital of one component 1,3,5-positions, resembles the behavior of the parent sys-
with the π*-orbital of the other (Figure 2, bottom). As dis- tem – in solution as well as in the crystalline state. A special
cussed for 14a, dimer 15a is not capable of further intramo- aspect is given by the threefold consecutive [2π+2π] cyclo-
lecular [2π+2π] photocycloaddition reactions.
addition of 7 which leads in anti-head-to-head processes to
[4.4.4](1,3,5)cyclophanes 8. The enone segments react
thereby selectively in the cisoid conformation. A related
photoreaction was used by Hasegawa et al.[26,27] for the to-
Conclusions
Photocyclodimerizations of the parent chalcone were al- pochemically controlled formation of [4.4](1,4)cyclophanes.
ready studied in the 1920s by Stobbe,[22,23] one of the early The presence of cinnamic acid or ester units in cyclophanes
pioneers in photochemistry. However, structures of the di- can be used to close further bridges between the decks.[28]
mers, obtained in solution, in the crystalline state and in
The opposite orientation of the enone units in 13 does
the melt,[24] led to a very long and controversial discussion, not yield [2.2.2](1,3,5)cyclophanes. After the first anti-head-
Eur. J. Org. Chem. 2007, 1983–1990
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E. Karpuk, D. Schollmeyer, H. Meier
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1H NMR (CDCl3): δ = 2.74 (s, 3 H, CH3), 3.90 (s, 6 H, p-OCH3),
3.93 (s, 12 H, m-OCH3), 6.89 (s, 4 H, o-H, trimethoxyphenyl), 7.48/
7.81 (AB, 3J = 15.6 Hz, 4 H, olefin. H), 8.66 (“s”, 2 H, o-H,
phenyl), 8.76 (“s”, 1 H, p-H, phenyl) ppm. 13C NMR (CDCl3): δ
= 27.0 (CH3), 56.4 (m-OCH3), 61.1 (p-OCH3), 106.2 (o-CH, tri-
methoxyphenyl), 120.0 (C-2), 129.8 (i-C, trimethoxyphenyl), 131.6,
132.1 (CH, phenyl), 137.8, 139.1 (Cq, phenyl), 141.1 (p-CqO), 146.8
(C-3), 153.6 (m-CqO), 188.9 (C-1), 197.1 (CO, acetyl) ppm. FD
MS: m/z (%) = 561 (100) [M + H+] C32H32O9 (560.2): calcd. C
68.56, H 5.75; found C 68.45, H 5.89.
to-head cycloaddition 13 Ǟ 14, the intramolecular mobility
is too low and the distance between the remaining double
bonds too large to permit further intramolecular [2π+2π]
photocycloadditions.
The crystalline states of 7a and 13a are capable of ef-
ficient single syn-head-to-tail cycloadditions – even when
the distance between the olefinic double bonds in neigh-
boring molecules exceeds with 5.07 Å by far the value of
4.2 Å proposed in Schmidt’s rule. We explain this result by
the fact, that the planes of the C=C double bonds are paral-
lel and have a short distance of 1.46 Å, which permits a
sufficient overlap of the π- and the π*-orbitals.
(E)-1-{3,5-Bis[(E)-3-(3,4,5-trimethoxyphenyl)acryloyl]phenyl}-3-
(3,4,5-trimethoxyphenyl)propenone (7b): Yellowish solid, m.p.
1
208 °C. H NMR (CDCl3): δ = 3.91 (s, 9 H, p-OCH3), 3.94 (s, 18
3
H, m-OCH3), 6.91 (s, 6 H, o-H, trimethoxyphenyl), 7.52 (d, J =
15.4 Hz, 3 H, olefin. H), 7.84 (d, 3J = 15.4 Hz, 3 H, olefin. H),
8.83 (s, 3 H, aromat. H, central benzene ring) ppm. 13C NMR
(CDCl3): δ = 56.4 (m-OCH3), 61.0 (p-OCH3), 106.2 (o-CH, tri-
methoxyphenyl), 120.2, 146.8 (olefin. CH), 129.8 (i-C, trimethoxy-
phenyl), 131.7 (aromat. CH, central benzene ring), 139.2 (Cq, cen-
tral benzene ring), 141.1 (p-CqO), 153.6 (m-CqO), 189.0 (CO) ppm.
FD MS: m/z (%) = 739 (100) [M + H+]. HR MS: calcd. for
[C42H42O12 + Na+] 761.2574; found 761.2468.
Experimental Section
General Remarks: UV/Vis: Zeiss MCS 320/340, CH2Cl2 as solvent.
1H and 13C NMR: Bruker AMX 400, CDCl3/TMS as internal stan-
dard. MS: Finnigan MAT 95 (FD, accelerating voltage 5 kV),
Micromass QTOF Ultima-3 (ESI, reference: CsI/NaI standard
solution), DSC: Perkin–Elmer DSC7. Melting points: Stuart Scien-
tific SMP/3; values uncorrected.
(E)-1-{3,5-Bis[(E)-3-(3,4,5-trihexyloxyphenyl)acryloyl]phenyl}-3-
(3,4,5-trihexoxyphenyl)propenone (7c): Preparation analogous to 7a.
After 1 d of stirring in the dark, the solution was neutralized with
HCl and extracted with CH2Cl2. The organic layer was washed
with saturated aqueous NaCl solution and H2O, dried with
MgSO4, and the solvents were evaporated. Column chromatog-
raphy (3ϫ40 cm SiO2; gradient toluene/ethyl acetate, 10:0 to 10:1)
yielded 268 mg (18%) of a yellowish solid which showed a single
phase transition in the DSC at 169.0 °C (onset temperature, heating
(E)-1-{3,5-Bis[(E)-(3-phenylacryloyl)]phenyl}-3-phenylpropenone [all-
(E)-1,3,5-Tricinnamoylbenzene (7a)]: Preparation according to the
1
literature,[10,11] yield 1.8 g (70%), m.p. 179 °C. H NMR (CDCl3):
3
δ = 7.45 (m, 9 H, m-H, p-H, phenyl), 7.65 (d, J = 15.6 Hz, 3 H,
2-H), 7.70 (m, 6 H, o-H, phenyl), 7.93 (d, 3J = 15.6 Hz, 3 H, 3-H),
8.84 (s, 3 H, aromat. H, central benzene ring) ppm. 13C NMR
(CDCl3): δ = 121.1 (C-2), 128.8, 129.1 (o-, m-CH, phenyl), 131.1,
131.8 (aromat. CH, p-C, phenyl and central benzene ring), 134.5
(i-C, phenyl), 139.1 (Cq, central benzene ring), 146.4 (C-3), 188.9
(C-1) ppm. FD MS: m/z (%) = 469 (100) [M + H+]. HR MS: calcd.
1
curve with a rate of 10 °Cmin–1. H NMR (CDCl3): δ = 0.90 (m,
27 H, CH3), 1.33–1.40 (m, 54 H, CH2) 1.77 (m, 18 H, CH2), 4.00
for C33H34O3 468.1725; found 468.1708. UV/Vis (CH2Cl2): λmax
=
(m, 18 H, OCH2), 6.90 (s, 6 H, o-H, trihexyloxyphenyl), 7.49 (d, 3J
326 nm; εmax = 69040 cm mmol–1.
3
= 15.6 Hz, 3 H, 2-H), 7.88 (d, J = 15.6 Hz, 3 H, 3-H), 8.77 (s, 3
H, aromat. H, central benzene ring) ppm. 13C NMR (CDCl3): δ =
13.0, 13.0 (CH3), 21.8, 25.0, 28.6, 29.6, 31.0 (CH2, partly superim-
posed) 68.5 (m-OCH2), 72.8 (p-OCH2), 106.5 (o-CH, trihexyloxy-
phenyl), 119.6, 145.8 (olefin. CH), 128.8 (i-C, trihexyloxyphenyl),
130.6 (aromat. CH, central benzene ring), 138.7 (Cq, central ben-
zene ring), 140.4 (p-CqO), 152.7 (m-CqO), 188.4 (CO) ppm. FD
MS: m/z (%) = 1369 (100) [M+·]. HR MS (ESI): calcd. for
[C87H132O12 + Na+] 1391.9617; found 1391.9585. UV/Vis
(CH2Cl2): λmax = 365 nm; εmax = 64905 cm mmol–1.
Condensation Reaction of 1,3,5-Triacetylbenzene (5) with 3,4,5-Tri-
methoxybenzaldehyde (6b): Ketone 5 (0.57 g, 2.8 mmol) and NaOH
(128 mg, 3.2 mmol) were warmed in C2H5OH (40 mL)/H2O
(60 mL) to 40 °C before aldehyde 6b (2.74 g, 14.0 mmol), dissolved
in C2H5OH (20 mL), was slowly added. The colorless solution
turned orange-red and a solid precipitated. After 5 h of stirring at
40 °C, CHCl3 was added so that the precipitate was dissolved. The
organic layer was washed with the same amount of H2O and satu-
rated aqueous NaCl solution, dried with MgSO4, and the solvents
were evaporated. Column chromatography (3ϫ50 cm SiO2; tolu-
ene/ethyl acetate, 9:1) yielded excess 6b, 264 mg (25%) of monocon-
densation product, 306 mg (20%) of dicondensation product and
71 mg (3%) of tricondensation product 7b.
(E)-1-{3,5-Bis[(E)-3-(3,4,5-tridodecyloxyphenyl)acryloyl]phenyl}-3-
(3,4,5-tridodecyloxyphenyl)propenone (7d): Preparation and workup
as described for 7c. Yield 354 mg (30%) of a yellowish waxy solid,
which showed in the DSC a transition to the isotropic phase at
123.7 °C (onset temperature, 2nd heating curve, rate: 10 °Cmin–1).
The 2nd heating curve contains two further overlapping peaks with
maxima at 20 and 27 °C which might point to an LC phase. 1H
NMR (CDCl3): δ = 0.85 (m, 27 H, CH3), 1.24–1.46 (m, 162 H,
CH2) 1.78 (m, 18 H, CH2), 4.00 (m, 18 H, OCH2), 6.87 (s, 6 H, o-
H, tridodecyloxyphenyl), 7.46 (d, 3J = 15.2 Hz, 3 H, 2-H), 7.80 (d,
3J = 15.2 Hz, 3 H, 3-H), 8.80 (s, 3 H, aromat. H, central benzene
ring) ppm. 13C NMR (CDCl3): δ = 14.1, 14.1 (CH3), 22.7, 26.1,
29.7, 29.7, 32.0 (CH2, partly superimposed) 69.4 (m-OCH2), 73.7
(p-OCH2), 107.6 (o-CH, tridodecyloxyphenyl), 119.9, 147.2 (olefin.
CH), 126.9 (i-C, tridodecyloxyphenyl), 129.4 (aromat. CH, phenyl),
139.4 (Cq, central benzene ring), 141.5 (p-CqO), 153.5 (m-CqO),
(E)-1-(3,5-Diacetylphenyl)-3-(3,4,5-trimethoxyphenyl)propenone:
1
Yellowish solid, m.p. 154 °C. H NMR (CDCl3): δ = 2.71 (s, 6 H,
CH3), 3.89 (s, 3 H, p-OCH3), 3.91 (s, 6 H, m-OCH3), 6.88 (s, 2 H,
o-H, trimethoxyphenyl), 7.43/7.79 (AB, 3J = 15.6 Hz, olefin. H),
8.69 (“s”, 1 H, p-H, phenyl), 8.70 (“s”, 2 H, o-H, phenyl) ppm. 13
C
NMR (CDCl3): δ = 26.9 (CH3), 56.4 (m-OCH3), 61.0 (p-OCH3),
106.2 (o-CH, trimethoxyphenyl), 120.0 (C-2), 129.8 (i-C, trimeth-
oxyphenyl), 131.4 (p-CH, phenyl), 131.9 (o-CH, phenyl), 141.1 (p-
CqO, trimethoxyphenyl), 146.8 (C-3), 153.6 (m-CqO, trimethoxy-
phenyl), 188.7 (C-1), 196.8 (CO, acetyl) ppm. FD MS: m/z (%) =
383 (100) [M + H+]. C22H22O6 (382.1): calcd. C 69.10, H 5.80;
found C 69.45, H 5.86.
(E)-1-{3-Acetyl-5-[(E)-3-(3,4,5-trimethoxyphenyl)acryloyl]phenyl}-3- 189.3 (CO) ppm. FD MS: m/z (%) = 2127 (100) [M+·]. HR MS
(3,4,5-trimethoxyphenyl)propenone: Yellowish solid, m.p. 134 °C.
(ESI): calcd. for [C141H240O12 + Na+] 2148.8068; found 2148.7986.
1988
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1983–1990

Cyclophanes from 1,3,5-Trisubstituted Benzenes
FULL PAPER
Irradiation of 7a in Solution: A solution of 7a (50 mg, 0.11 mmol)
in CH2Cl2 (or CD2Cl2) (0.75 mL) was irradiated with a high-pres-
sure QSL lamp equipped with a Pyrex filter for 1.5 h. Addition of
petroleum ether (b.p. 40–60 °C) (5 mL) yielded 29 mg (58 %) of
pure cyclophane 8a (structure 8ab) which melted at 248 °C (de-
comp.). 1H NMR (CDCl3): δ = 3.90/4.47 (AAЈBBЈ, 12 H, cyclobu-
tane rings), 7.20–7.40 (AAЈBBЈC, 30 H, phenyl groups), 7.81 (s, 6
H, aromat. H, central benzene rings) ppm. 13C NMR (CDCl3): δ
= 41.7 (β-C, cyclobutane), 52.9 (α-C, cyclobutane), 127.0 (o-CH,
phenyl), 128.9 (m-CH, phenyl), 127.4 (p-CH, phenyl), 131.4 (CH,
central benzene ring), 140.4, 140.6 (i-C, phenyl and Cq, central ben-
zene ring), 197.8 (CO).[29] The same irradiation of a less concen-
trated solution (2.9ϫ10–2 , CD2Cl2) was used for the determi-
nation of the photochemically formed isomers of 7a/(E,E,E)/
(E,E,Z)/(E,Z,Z)/(Z,Z,Z) = 2:4:8:5. The integration of the 1H NMR
signals of the protons on the central benzene ring (the A3 and A2M
spin patterns between δ = 8.5 and 8.9 ppm) served for the quantita-
tive determination.
491.1623; found 491.1642. UV/Vis (CH2Cl2): λmax = 311 nm; εmax
= 74160 cm mmol–1.
(E,E,E)-1,3,5-Tris[3-oxo-3-(3,4,5-trimethoxyphenyl)propen-1-yl)ben-
zene (13b): Preparation as described for 13a yielded 280 mg (38%)
of product which still contained some impurities. Column
chromatography (3ϫ30 cm Al2O3, CHCl3) gave 110 mg (15%) of
highly pure yellowish solid, which melted at 98 °C. 1H NMR
(CDCl3): δ = 3.91 (s, 9 H, OCH3), 3.92 (s, 18 H, OCH3), 7.26 (s, 6
3
H, aromat. H, outer benzene rings), 7.56/7.82 (AB, J = 15.8 Hz,
6 H, olefin. H), 7.86 (s, 3 H, aromat. H, central benzene ring) ppm.
13C NMR (CDCl3): δ = 56.5 (6 OCH3), 61.0 (3 OCH3), 106.2 (aro-
mat. CH, outer benzene rings), 123.4 (β-CH), 129.4 (HC-2,
phenyl), 132.9 (Cq, outer benzene rings), 136.5 (C-1), 142.7 (α-CH),
142.9, 153.2 (CqO), 188.6 (CO) ppm.[29] FD MS: m/z (%) = 739
(100) [M + H+]. HR MS (ESI): calcd. for [C42H42O12 + Na+]
761.2574; found 761.2563.
Irradiation of 13a in Solution: A solution of 13a (150 mg,
0.32 mmol) in CH2Cl2 (3.3 mL) (c = 9.7ϫ10–2 ) was irradiated
with a QSL lamp equipped with a Pyrex filter for 3 h. The obtained
oligomer mixture was purified by column chromatography
(2ϫ30 cm SiO2; CH2Cl2/H3CCOOC2H5, 20:1). The first fractions,
which contained 14a and low oligomers, were then used for prepar-
ative TLC [20ϫ20 cm SiO2; petroleum ether (b.p. 40–60 °C)/diethyl
ether, 1:3]. Pure dimer 14a was obtained in a yield of 7 mg per
TLC plate (yield 6%). It is an almost colorless solid which starts to
decompose at 200 °C. 1H NMR (CDCl3): δ = 4.14/4.65 (AAЈBBЈ, 4
H, cyclobutane ring), 7.86/7.34/7.59 (AAЈBBЈC, 10 H, benzoyl
groups on cyclobutane), 7.98/7.50/7.56 (AAЈBBЈC, 20 H, aromat.
Irradiation of a 2: 1 Mixture of 7a/7b: Irradiation and workup as
described for 7a. The product mixture had a ratio of 9/8b/8a =
77:19:Յ4 according to the 1H NMR spectrum. Since 9 is by far the
major product, the mixture could be directly used for the NOE
measurement.
Irradiation of 7a in the Crystalline State: 7a (260 mg, 0.56 mmol)
was crystallized from the melt on a 10ϫ10 cm glass plate and irra-
diated with a Hanovia 450 W lamp equipped with a Pyrex filter.
At the end of the reaction (TLC control: SiO2; toluene/ethyl ace-
tate, 50:1), the material was flushed in CHCl3. After evaporation
of the solvent, portions of 30 mg of the residue were purified by
preparative TLC (20ϫ20 cm SiO2; toluene/ethyl acetate, 50:1).
Each portion yielded 20 mg (66%) of a colorless solid 10a which
melted at 190 °C. 1H NMR (CDCl3): δ = 4.94/5.16 (AAЈBBЈ, 4
H, cyclobutane, 7.30/7.12/7.01 (AAЈBBЈC, 10 H, phenyl groups on
cyclobutane ring), 7.68/7.45/7.45 (AAЈBBЈC, 20 H, phenyl groups
on olefinic double bonds), 7.52/7.87 (AB, 3J = 15.8 Hz, 4 H, olefin.
H), 8.46/8.67 (A2B, 4J = 1.5 Hz, central benzene rings) ppm. 13C
NMR (CDCl3): δ = 42.3 (β-C, cyclobutane), 51.2 (α-C, cyclobu-
tane), 120.9, 146.3 (olefin. CH), 127.4 (p-CH, phenyl groups on
cyclobutane), 128.2 (o-CH, phenyl groups on cyclobutane), 128.5
(m-CH, phenyl groups on cyclobutane), 128.7 (o-CH, phenyl
groups on olefinic double bonds), 129.0 (m-CH, phenyl groups on
olefinic double bonds), 131.1 (p-CH, phenyl groups on olefinic
double bonds), 131.4/131.7 (CH, central benzene ring), 134.4 (i-C,
phenyl groups on olefinic double bonds), 137.4 (i-C, phenyl groups
on cyclobutane), 138.4, 138.6 (Cq, central benzene ring), 188.6 (CO,
cinnamoyl), 197.7 (CO) ppm.[29] FD MS: m/z (%) = 936 (100)
[M+·]. HR MS (ESI): calcd. for [C66H48O6 + Na+] 959.3349; found
959.3353.
3
H, benzoyl groups on olefinic double bonds), 7.59/7.77 (AB, J =
15.8 Hz, 8 H, olefin. H), 7.61 (m, 4 H, aromat. H, central benzene
ring), 7.79 (m, 2 H, aromat. H, central benzene ring) ppm. 13C
NMR (CDCl3): δ = 46.8, 47.7 (CH, cyclobutane ring), 123.5, 143.2
(olefin. CH), 127.3, 129.8 (aromat. CH, central benzene ring),
128.6, 128.7, 133.0 (aromat. CH, benzoyl group on olefinic double
bond), 128.8, 128.9, 134.0 (aromat. CH, benzoyl group on cyclobu-
tane ring), 135.2, 136.4 (aromat. Cq, central benzene ring), 137.8,
142.8 (aromat. Cq, benzoyl groups), 190.1 (CO, enone), 198.4 (CO)
ppm. FD MS: m/z (%) = 938 (100) [M+·]. HR MS (ESI): calcd. for
[C66H48O6 + Na+] 959.3349; found 959.3364.
Irradiation of 13a in the Crystalline State: 13a (66 mg, 0.14 mmol)
was irradiated as described for 7a. The obtained dimer 15a (38 mg,
57%) is an almost colorless solid which starts to decompose above
1
120 °C. H NMR (CDCl3): δ = 4.95/5.65 (AAЈBBЈ, 4 H, cyclobu-
tane ring), 7.77/7.32/7.40 (AAЈBBЈC, 10 H, aromat. H, benzoyl
3
group on cyclobutane ring), 7.42/7.66 (AB, J = 15.8 Hz, 4 H, ole-
fin. H), 8.01/7.53/7.61 (AAЈBBЈC, 20 H, aromat. H, benzoyl group
on olefinic double bond), 7.55 (m, 6 H, aromat. H, central benzene
ring) ppm. 13C NMR (CDCl3): δ = 42.0 (β-CH, cyclobutane), 50.0
(α-CH, cyclobutane), 123.2, 143.4 (olefin. CH), 126.9, 129.6 (aro-
mat. CH, central benzene ring), 128.2, 128.6, 133.5 (CH, benzoyl
group on cyclobutane ring), 128.6, 128.7, 133.0 (CH, benzoyl group
on olefinic double bond), 135.7, 136.3, 137.9, 140.3 (aromat. Cq),
190.2 (CO, enone), 198.2 (CO) ppm.[27] FD MS: m/z (%) = 937 (84)
[M + H+], 469 (100) [M + 2 H+·]. HR MS (ESI): calcd. for
[C66H48O6 + Na+] 959.3349; found 959.3324.
(E,E,E)-1,3,5-Tris(3-oxo-3-phenylpropen-1-yl)benzene (13a): A mix-
ture of trialdehyde 11 (162 mg, 1.0 mmol), acetophenone 12a
(420 mg, 3.5 mmol) and KOH (28 mg, 0.5 mmol) in dry methanol
(11 mL) was stirred in the presence of 4-Å molecular sieves at ambi-
ent temperature. A colorless precipitate was formed and the reac-
tion was stopped after 24 h. The solid was recrystallized from di-
ethyl ether to which ethanol was added until the boiling solution
became turbid. Yield 282 mg (60%), m.p. 194 °C (ref.[12] 187 °C).
1H NMR (CDCl3): δ = 8.04/7.51/7.58, m, 3 H (AAЈBBЈ, 15 H,
aromat. H, phenyl), 7.62/7.82 (AB, 3J = 15.8 Hz, 6 H, olefin. H)
Crystal Structure Analysis of 13a: The measurements were carried
out with an Enraf–Nonius CAD-4-diffractometer with the software
Collect V5 (Enraf–Nonius B.V., Delft, The Netherlands, 1989). The
ppm. 13C NMR (CDCl3): δ = 123.8 (β-CH), 128.6, 128.7 (o-CH, structure was solved with SIR 92[30] and refined by full-matrix le-
m-CH, phenyl), 129.4 (HC-2), 133.1 (p-CH, phenyl), 136.5, 137.8
ast-squares technique on F2 with SHELXL-97.[31] Details on the
(aromat. Cq), 142.9 (α-CH), 190.0 (CO) ppm.[29] FD MS: m/z (%) X-ray crystal structure analysis are listed in Table 2. CCDC-634439
= 469 (100) [M + H+]. HR MS (ESI): calcd. for [C33H24O3 + Na+] contains the supplementary crystallographic data for this paper.
Eur. J. Org. Chem. 2007, 1983–1990
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1989

E. Karpuk, D. Schollmeyer, H. Meier
FULL PAPER
[6] For the photochemical synthesis of cyclophanes, see for exam-
ple: J. Nishimura, Y. Nakamura, Y. Hayashida, T. Kudo, Acc.
Chem. Res. 2000, 33, 679–686; J. Nishimura, Y. Nakamura, T.
Yamazaki, S. Inokuma in CRC Handbook of Organic Photo-
chemistry and Photobiology, 2nd ed. (Eds.: W. Horspool, F.
Lenci), CRC Press, Boca Raton, 2004.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data-
request/cif.
Table 2. Details of the X-ray crystal structure analysis of (E,E,E)-
1,3,5-tris(3-oxo-3-phenylpropenyl)benzene (13a).
[7] See however M. A. Kinder, P. Margaretha, Org. Lett. 2000, 2,
4253–4255.
Empirical formula
Formula mass
Habit
Crystal size [mm]
Space group
Cell constants:
a [Å]
C33H24O3·CHCl3
587.9
yellow block
0.2ϫ0.25ϫ0.4
P21/c (monoclinic)
[8] H. Meier, E. Karpouk, Tetrahedron Lett. 2004, 45, 4477–4480.
[9] Due to the 1,3,5-trisubstitution, the chalcone units can be re-
garded in the first approximation as independent chromo-
phores.
[10] S. V. Tsukerman, E. V. Danilchenko, V. M. Nikitchenko, V. F.
Lavrushin, Khim. Geterotsikl. Soedin. 1974, 1394–1397 [Chem.
Abstr. 1975, 82, 43245u].
[11] S. V. Tsukerman, E. V. Danilchenko, V. M. Nikitchenko, V. F.
Lavrushin, J. Org. Chem. USSR (Engl. Transl.) 1974, 10,
2643–2644; Zh. Org. Khim. 1974, 10, 2623–2624.
[12] The parent system trans-chalcone (trans-1,3-diphenylpro-
penone) has a λmax value of 309 nm.
7.810(3)
34.241(3)
10.645(4)
90.98(2)
2846(2)
4
1.372
Cu-Kα
3.19
b [Å]
c [Å]
β [°]
V [Å3]
Z
DX [Mgm–3]
Radiation
µ [mm–1]
[13] MestRe-C2.3a Software.
3
[14] Compound 8ab contains only J(trans) couplings, whereas 8ac
3
3
contains J(cis) and J(trans) couplings in the four-membered
rings. However, the obtained coupling constants of 9.95 and
8.95 Hz are too similar to permit a decision between 8ab and
8ac.
F(000)
T [K]
Θmax [°]
No. of reflections:
measured
independent
observed [|F|/σ(F) Ͼ 4.0]
Rσ
1216
193
74
[15] E. Karpouk, Dissertation, Mainz, 2004.
6202
5771
4336
0.0288
379
0.1617
0.0583
1.042
0.43
[16] V. A. Dombrovskii, L. A. Yanovskaya, Bull. Acad. Sci. USSR,
Div. Chem. Sci. (Engl. Transl.) 1975, 24, 2503–2504; Izv. Akad.
Nauk SSSR Ser. Khim. 1975, 24, 2613–2614.
[17] W. Winter, U. Langjahr, H. Meier, J. Merkushew, J. Juriew,
Chem. Ber. 1984, 117, 2452–2463.
[18] R. Petermann, C. Schnorpfeil, M. Lehmann, M. Fetten, H.
Meier, J. Inf. Rec. 2000, 25, 259–264.
[19] H. Meier, M. Lehmann in Encyclopedia of Nanoscience and
Nanotechnology (Ed.: H. S. Nalwa), American Scientific Pub-
lisher, Stevenson Ranch, CA, 2004, vol. 10, pp. 95–106.
[20] The three C=C double bonds in 13 can adopt (as in 1,3,5-
trivinylbenzene) a C3h arrangement (shown in Scheme 6) or a
Cs arrangement.
[21] G. M. J. Schmidt, Pure Appl. Chem. 1971, 27, 647–678.
[22] H. Stobbe, A. Hensel, Ber. Dtsch. Chem. Ges. 1926, 59, 2254–
2265.
Parameters
wR (F2, all reflections)
R [F2, Ͼ2σ(F2)]
S
Max. ∆ρ [eÅ–3]
Min. ∆ρ [eÅ–3]
–0.57
Acknowledgments
We are grateful to the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie for financial support.
[23] H. Stobbe, K. Bremer, J. Prakt. Chem. 1929, 123, 1–60.
[24] F. Toda, K. Tanaka, M. Kato, J. Chem. Soc., Perkin Trans. 1
1998, 1315–1318.
[25] For the first clear decision, see S. Caccamese, J. A. McMillan,
G. Montaudo, J. Org. Chem. 1978, 43, 2703–2704.
[26] M. Hasegawa, M. Nohara, K. Saigo, T. Mori, H. Nakanishi,
Tetrahedron Lett. 1984, 25, 561–564.
[27] M. Hasegawa, K. Saigo, T. Mori, H. Uno, M. Nohara, H.
Nakanishi, J. Am. Chem. Soc. 1985, 107, 2788–2793.
[28] For example, see: U. Meyer, N. Lahrahar, P. Marsau, H. Hopf,
H. Greiving, J.-P. Desvergne, H. Bouas-Laurent, Liebigs Ann./
Recueil 1997, 381–384; H. Greiving, H. Hopf, P. G. Jones, P.
Bubenitschek, J.-P. Desvergne, H. Bouas-Laurent, Liebigs
Ann.Chem. 1995, 1949–1956.
[29] The assignment is based on 2D-NMR measurements (HMQC
and HMBC).
[30] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi,
M. C. Burla, G. Polidori, M. Camalli, J. Appl. Crystallogr.
1994, 27, 435.
[1] C. J. Brown, A. C. Farthing, Nature 1949, 164, 915.
[2] D. J. Cram, J. Steinberg, J. Am. Chem. Soc. 1951, 73, 5691–
5704.
[3] Selected books and review articles: a) Modern Cyclophane
Chemistry (Eds.: R. Gleiter, H. Hopf), Wiley-VCH, Weinheim,
2004; b) F. Vögtle, Cyclophane Chemistry: Synthesis Structures
and Reactions, Wiley-VCH, Chichester, 1999; c) F. Diederich,
Cyclophanes, Royal Society of Chemistry, Cambridge, 1991; d)
P. M. Keehn, S. M. Rosenfeld, Cyclophanes, Academic Press,
New York, 1983, 2 vols.; e) B. König, Top. Curr. Chem. 1998,
196, 91–136; f) F. Vögtle, Top. Curr. Chem. 1983, 113; g) F.
Vögtle, Top. Curr. Chem. 1983, 115.
[4] E. Müller, H. Meier, M. Sauerbier, Chem. Ber. 1970, 103, 1356–
1363.
[5] See also J. Juriew, E. Merkuschew, T. Skorochodowa, W. Win-
ter, H. Meier, Angew. Chem. 1981, 93, 285–286; Angew. Chem.
Int. Ed. Engl. 1981, 20, 269–270, H. Meier, J. Juriew, W. Winter,
J. Photochem. 1981, 17, 1272.
[31] G. M. Sheldrick, SHELXL-97, Program for crystal structure re-
finement, University of Göttingen, Germany, 1997.
Received: January 4, 2007
Published Online: March 2, 2007
1990
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1983–1990