Cyclophane size drives the photochemical behaviour of benzophenone

Article abstract of DOI:10.1039/c2pp25025j

A new series of all-heterahomocalixarene-type structures was prepared. The new hetera[2_n]metacyclophanes obtained contain a benzophenone moiety as photoactive component. Although both forms possess identical building blocks and differ only in r

Full text of DOI:10.1039/c2pp25025j

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PAPER
Cyclophane size drives the photochemical behaviour of benzophenone†‡
Yolanda Vidaa,b and Ezequiel Perez-Inestrosa*a,b
Received 31st January 2012, Accepted 1st March 2012
DOI: 10.1039/c2pp25025j
A new series of all-heterahomocalixarene-type structures was prepared. The new hetera[2n]-
metacyclophanes obtained contain a benzophenone moiety as photoactive component. Although both
forms possess identical building blocks and differ only in ring size, they are markedly different in
photochemical reactivity. The cyclophane size is the driving force for the photochemical behaviour of the
benzophenone.
more flexible carbocyclic scaffold. The relatively rigid skeleton
of all-homocalixarenes, where the bridging chains are elongated
Introduction
As reflected in the construction of a large variety of macromol-
ecules,1 the design and synthesis of macrocyclic compounds has
been one of the driving forces for the development of supramole-
cular science. Of special interest in this respect are cyclophanes,2
which are macrocycles containing aromatic groups, and, particu-
larly, calixarene-like structures, which possess unique physical
properties and are highly suitable model compounds for studying
intramolecular processes3 and host–guest chemistry.4 Calix[n]-
arenes are [1n]metacyclophanes that are easily synthesized and
can be readily functionalized.5 They are considered as the third
generation of synthetic receptors in addition to crown ethers and
cyclodextrins. Their high level of pre-organization, well-known
conformational preferences and cavity structure have fostered a
wide use as molecular platforms and host molecules in supramo-
lecular chemistry. Besides the fundamental carbon-bridge calix-
arene skeletons, several other families of related macrocycles
have emerged in the last few decades which have been named in
accordance with cyclophane nomenclature: heterocalixarenes
(calixpyrroles, calixfurans),6,7 where heteroaromatic arene units
are incorporated into the structure; heteracalixarenes (aza- or
oxacalix[n]arenes),8,9 where the aromatic units are linked by a
heteroatom; and heterocalixaromatics [heteroatom-bridged calyx-
(hetero)arenes],10,11 which exhibit both types of heteroatom
substitution.
by one atom, can adopt a more flexible molecular architecture
and prevent the formation of unfavourable stable conformers in
solution.12 Homoheterocalixaromatics were recently obtained by
inserting a methylene unit at some of the bridging positions of a
heterocalixaromatic.13 These modifications of classic macro-
cycles has facilitated the synthesis of a new family of com-
pounds where ring size, which is directly related to cavity size,
can be easily tuned and as a consequence the properties of the
molecules too. The electronic structure and geometric confor-
mation of the ensuing supramolecular structures are certainly
related. The photophysical and photochemical properties of a
chromophore are influenced by its environment, which can there-
fore be used to modulate them.14 Environmental properties15,16
and molecular geometry17 have been shown to alter absorption
transitions and even the photochemical reactivity of benzophe-
none, which has been the subject of thorough study.18
This paper reports the synthesis of the all-heterahomocalixar-
enes 1 and 2 (Scheme 1) by incorporating a benzophenone unit
into the macrocycle to obtain two photoactive cyclophanes. The
building blocks used for this purpose were identical except in
number. As a result, 1 and 2 possess the same scaffolds but
differ significantly in ring size. The resulting differences in
cavity size affect not only the stiffness of the molecular skeleton,
but also all related properties. The photochemical reactivity of
both macromolecules, which contain benzophenone as their sole
photoactive component, was assessed and found to be influenced
by the degree of structural organization and ring size.
These new compound families differ in size, conformational
preferences and electronic configuration, which may help expand
the scope of classical calixarene chemistry. Special interest has
been aroused by similar systems based on a conformationally
Results and discussion
aBIONAND-Andalusian Center for Nanomedicine and Biotechnology,
Parque Tecnológico de Andalucía, 29590 Málaga, Spain
bDepartment of Organic Chemistry, Faculty of Sciences, University of
Malaga, Malaga, Spain. E-mail: inestrosa@uma.es; Fax: +34 952
133433; Tel: +34 952 137565
†This article is published as part of a themed issue in honour of
Jean-Pierre Desvergne on the occasion of his 65th birthday.
‡Electronic supplementary information (ESI) available: Materials and
methods; NMR spectra; characterization of compounds. See DOI:
10.1039/c2pp25025j
All-heterahomocalixarenes 1 and 2 are [2n]metacyclophanes
where the ethylene bridges of the corresponding all-homocalix-
arenes have been symmetrically substituted by methyloxa
bridges. Both contain a photochemically active unit; unlike pre-
viously reported cyclophanobenzophenones,17 however, only
one of the benzene rings is incorporated into a calixarene cavity
skeleton. Although calixarene nomenclature is well established,
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Scheme 1 Synthetic route for macrocycles 1 and 2. General procedure: (i) TsCl (CH2Cl2 solution)/NaOH (H2O solution), TEBA, r.t., 12 h; (ii)
NaBH4, MeOH, r.t., 5 h; (iii) HBr (33 wt% in acetic acid), r.t., 3 h; (iv) 2,4-dihydroxybenzophenone, K2CO3, anhydrous acetone, 60 °C, 24 h; (v)
KOH, MeOH, 65 °C, 3 h; (vi) α,α′-dibromo-p-xylene, K2CO3, anhydrous acetone, 60 °C, 72 h.
the complexity of these new, related compounds led us to switch
to phane nomenclature. Note that the atom numbering in the
structures of 1 and 2 is that adopted by IUPAC (see ESI†).19,20
Synthesis of cyclophanes 1 and 2
Both cyclophanes (Scheme 1) were synthesized from 3-hydroxy-
benzaldehyde. Protection of the phenol group, reduction to
benzyl alcohol and subsequent bromination yielded the corre-
sponding bromoderivative 3. Cyclophane 1 was synthesized by
condensation of 2,4-dihydroxybenzophenone with two units of
3, followed by deprotection of the phenol groups. Following
similar previously-reported procedures,21,22 2,4-bis[3′-(hydroxyl)
benzyloxy]benzophenone (4a) was then reacted with α,α′-
dibromo-p-xylene under high dilution conditions in the presence
of K2CO3 to obtain 1 with a 54% yield. A similar synthetic strat-
egy was used to obtain 2. Thus, condensation of 2,4-dihydroxy-
Fig. 1 Electronic absorption spectra for 1 and 2 (solid line), 2,4-
benzophenone with one equivalent of 3, followed by
dimethoxybenzophenone (solid line with circles), 3-methoxybenzyl
methyl ether (dashed line) and p-xylene (dashed–dotted line).
deprotection of phenol groups, gave 2-hydroxy-4-[3′-(hydroxy)
benzyloxy]benzophenone (4b). The high yield of the reaction
and the virtual absence of by-products can be ascribed to the
differential reactivity of the two hydroxyl groups in 2,4-dihy-
droxybenzophenone: the o-hydroxyl group to carbonyl forms an
intramolecular hydrogen bond and becomes less reactive as a
result. Cyclization of 4b with α,α′-dibromo-p-xylene under
similar conditions as with 1 gave 2 with a 47% yield.
The two compounds were characterized in structural terms.23
The 1H-NMR spectrum for cyclophane 1 confirmed the sym-
metry of its internal cavity. Assigning signals required using
Scheme 2 Photochemical reaction of 1 (10−3 M) in benzene, followed
by HCl treatment.
various experiments. Cyclophane
behaviour.
2 exhibited a similar
application of this reaction is the preparation of benzofurans.25
When the o-alkoxybenzophenone moiety is included in a large
macrocycle, the resulting benzofuranol is part of the macrocycle
too; this facilitates synthesis of these types of cyclophanes where
the enormous size of the ring cavity has no influence on their
photochemical reactivity.26 Since cyclophane 1 and 2 contain an
o-alkoxybenzophenone sub-unit, their photoirradiation should
give new cyclophanes containing the benzofuran ring in a rela-
tively small cavity. The photocyclization reaction of 1 is depicted
in Scheme 2. A solution of 1 in benzene was irradiated with a
medium-pressure mercury lamp under a nitrogen atmosphere for
25 min. Rather than attempting isolation and separation of dia-
stereoisomers of the initially benzohydrofuranol formed, the
Photochemical reactivity
Fig. 1 shows the electronic absorption spectra for both cyclo-
phanes in acetonitrile, as well as the absorption spectra for the
individual moieties present in their structures (2,4-dimethoxy-
benzophenone, 3-methoxybenzyl methyl ether and p-xylene).
The spectra for 1 and 2 are quite consistent with the combined
spectra for their constituent units; also, they are largely domi-
nated by the contribution of the 2,4-dimethoxybenzophenone
moiety.
o-Alkoxybenzophenones are known to photocyclize readily to
benzofuranols via intramolecular δ-hydrogen abstraction to form
the corresponding benzofuran by dehydration.24 One synthetic
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concentrated reaction mixture was treated with a few drops of
1 M HCl in acetone, which gave 5 (60%) as a white solid. The
photochemical reaction of 1 takes place through intramolecular
δ-hydrogen abstraction. After formation of a benzohydrofuranol
ring, dehydration gave the new cyclophane 5, which was fully
characterized and found to exhibit the typical fluorescence emis-
sion at 400 nm and a fluorescent quantum yield of 0.73 in
acetonitrile.
resin (CrO3–Amberlist A26)28 resulted in its quantitative conver-
sion into 7.
Irradiation of 2 led to the formation of a biradical intermediate
via intramolecular δ-hydrogen abstraction of a benzyloxy hydro-
gen by the carbonyl oxygen. This biradical intermediate should
undergo 1,5 cyclization to form the benzofuranol ring as in 1,
under certain conditions, however, it is subject to competing 1,3-
cyclization,27 which gives a spiro–epoxide intermediate sub-
sequently rearranging to the corresponding 2-acyl-benzyl alcohol
(6).
Irradiating 2 under the same conditions did not result in the
expected formation of a benzofuran ring. Although both cyclo-
phanes possess the same photochemically active sub-unit, their
photochemical reactivity differs significantly. The photoreaction
of 2 is depicted in Scheme 3. Irradiating a solution of 2 in
benzene for 25 min and subsequent work-up provided a mixture
of two compounds (6 and 7). Compound 7 was easily character-
The photoreactivity of the two cyclophanes differs in the be-
haviour of the 1,5-biradical formed. The efficiency of benzofura-
nol formation after intramolecular δ-hydrogen abstraction is
directly related to the ease of rotation about the aryl-C bond.29,30
In both cyclophanes, the benzophenone moiety is substituted
with benzoyl groups where the π-system is conjugated in the
triplet state. Therefore, the triplet 1,5-biradical is a fully conju-
gated benzyl radical site in both cases. However, rotation by
about 90° is required for cyclization to occur. This process is
delayed by the lack of conjugation in benzyloxyacetophenones.
However, this is not the case with benzyloxybenzophenones,
where compensatory rotation about the other benzyl bond pre-
serves benzylic conjugation.31 Based on this assumption, the bi-
radicals formed from both cyclophanes can rapidly rotate into
the conformation required for cyclization to a furanol ring. In 1,
where the macrocycle is large enough to allow rotation, this is
the preferential process and yields 5 as the sole product. In 2
(Scheme 4), rotation is unfavourable. The smaller size of the
macrocycle results in a less conformationally flexible cyclophane
and hence in restricted rotation. The conformational changes
required for cyclization place too much strain on the ring and
considerably delay the process as a result. No rotation about the
benzyl bond is required for the competing spirocyclization
process, however. The 1,5-biradical initially produced by exci-
tation of 2 therefore has more time to undergo this reaction,
which is thus the prevalent process.
1
ized. By contrast, 6 had an extremely complex H-NMR spec-
trum. Recrystallizing this compound considerably simplified its
spectrum, which, however, regained its complexity with time.
This is related with a conformational rearrangement of the
macromolecule in solution. We managed to fully characterize the
1H-NMR spectrum but not the 13C spectrum or other NMR
experiments. The assigned structure was confirmed by oxidation
of 6. Thus, treating a solution of 6 in benzene with an oxidant
Geometric factors imposed by the structure of a molecule are
known to determine the pathway of some reactions.32 In our
case, it is the size of the macrocycle that determines the
Scheme 3 Photochemical reaction of 2 (10−3 M) in benzene. Quanti-
tative oxidation of 6.
Scheme 4 Mechanism for the photoreaction of 2.
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particular photoreaction. Although both cyclophanes possess the
same kind of building block and photoactive subunit, their
photoreaction proceeds differently. Thus, the conformational
reorganization needed for cyclization is facilitated by the large
ring size of 1, but places too much strain on the ring in 2, which
causes the competing spirocyclization process to prevail.
131.9, 137.8, 145.8, 150.1, 190.6. m/z (MS-EI): 276 (M+, 50%),
155 (90), 91 (100), 65 (50).
3-(Tosyloxy)benzyl alcohol. NaBH4 (1.8 g, 46 mmol) was
added to a stirred solution of 3-(tosyloxy)benzaldehyde (12.8 g,
46 mmol) in methanol (150 mL) at 0 °C and allowed to react at
room temperature for 5 h. Dichloromethane was then added to
the reaction mixture, the organic layer being washed with water
and dried over MgSO4, and the solvent removed to obtain the
desired compound (96%) as a white solid. Mp 65–67 °C. δH
(200 MHz, CDCl3): 2.43 (3H, s, –CH3), 4.62 (2H, s, Ar–CH2–
OH), 6.84 (1H, m, H-4), 7.03 (1H, bs, H-2), 7.24 (2H, m, H-6,
H-5), 7.29 (2H, d, J = 8.1 Hz, Ts), 7.69 (2H, d, J = 8.1 Hz, Ts).
δC (50 MHz, CDCl3): 21.5, 63.9, 120.5, 120.9, 125.2, 128.3,
129.5, 129.7, 132.1, 143.1, 145.4, 149.5. m/z (MS-EI): 278
(M+, 7%), 155 (43), 91 (100), 65 (28).
Conclusions
As shown here, the photochemical reactivity of benzophenone
inserted into a cyclophane can be tuned via the cyclophane size.
Although the photoreaction of benzophenone inserted in a
macrocycle has been previously studied, the increased ring size
and decreased rigidity of the system resulting from the presence
of alkyl chains facilitates conformational changes. Our calix-
arene-type architecture exhibits a higher level of organization,
which significantly reduces rotational freedom. As a result,
changes in cavity size have a significant effect on the properties
of the inserted molecule.
A new class of hetera[2n]metacyclophanes has been prepared
where ring-size can be easily tuned with a view to modulating
the photoreactivity of inserted benzophenone. This provides a
method for obtaining luminescent hosts capable of photochemi-
cally trapping selective guests by using an appropriate combi-
nation of photoactive unit and ring size.
3-(Tosyloxy)benzyl bromide (3). A solution of 3-(tosyloxy)
benzyl alcohol (10 g, 36 mmol) in 100 mL of HBr (33 wt% sol-
ution in acetic acid) was stirred at room temperature for 3 h. A
saturated solution of K2CO3 in water was then added to neutral-
ize the mixture, which was extracted with dichloromethane. The
organic layer was then dried over anhydrous MgSO4 and the
solvent removed to obtain the desired compound (70%) as a
yellow solid. Mp 65–66 °C. δH (200 MHz, CDCl3): 2.43 (3H, s,
–CH3), 4.35 (2H, s, Ar–CH2–Br), 6.92 (2H, m, H-2, H-6), 7.26
(4H, m, H-4, H-5, Ts), 7.67 (2H, d, J = 8.2 Hz, Ts). δC
(50 MHz, CDCl3): 21.6, 31.9, 122.3, 122.9, 127.5, 128.3, 129.7,
129.8, 131.8, 139.5, 145.5, 149.4. m/z (MS-EI): 342 (M+ + 2,
4%), 340 (M+, 4%), 155 (35), 91 (100), 78 (40).
Experimental
Synthesis
2,4-Bis[3′-(tosyloxy)benzyloxy]benzophenone. A solution of 3
(1.43 g, 4.2 mmol), 2,4-dihydroxybenzophenone (428 mg,
2 mmol) and K2CO3 (1.66 g, 12 mmol) in anhydrous acetone
(20 mL) was refluxed for 24 h. Then, water (10 mL) was added
and the acetone removed from the reaction mixture. The aqueous
layer was extracted with dichloromethane and the organic layer
dried over anhydrous MgSO4 and filtered, the solvent being
removed to obtain the desired compound (98%) as a white solid.
Mp 118–120 °C. δH (400 MHz, CDCl3): 2.33 (3H, s, –CH3),
2.36 (3H, s, –CH3), 4.80 (2H, s, Ar′′–CH2–O–Ar), 4.98 (2H, s,
Ar′′′–CH2–O–Ar), 6.44 (1H, d, J = 2.3, H-3), 6.52 (1H, dd, J =
7.8, 2.3, H-5), 6.55 (1H, br s, H-2′′), 6.68 (1H, dd, J = 7.8, 2.3,
H-4′′), 6.73 (1H, d, J = 7.8, H-6′′), 6.81 (1H, dt, J = 7.8, 2.3,
H-4′′′), 7.01 (1H, t, J = 7.8, H-5′′), 7.11 (1H, br s, H-2′′′), 7.18
(3H, m, H-5′′′, Ts), 7.22 (3H, m, H-6′′′, Ts), 7.33 (2H, t, J = 7.8,
H-3′, H-5′), 7.40 (1H, d, J = 7.8, H-6), 7.45 (1H, t, J = 7.8,
H-4′), 7.57 (2H, d, J = 7.8, Ts), 7.65 (4H, m, H-2′, H-6′, Ts). δC
(50 MHz, CDCl3): 21.7, 69.2, 100.6, 106.3, 120.4, 121.3, 121.4,
121.8, 122.4, 124.9, 125.8, 128.2, 128.3, 128.4, 129.3, 129.5,
129.7, 129.8, 132.3, 132.6, 138.2, 138.4, 139.0, 145.4, 145.5,
149.5, 149.8, 158.0, 162.0, 195.6. m/z (MS-EI): 735 (M+, 3%),
474 (35), 261 (100), 105 (37). HRMS m/z found: 735.1707.
Calc. for C41H35O9S2 (M+) 735.1723.
All chemicals were commercially available products and used as
received. 2,4-Dihydroxybenzophenone and α,α′-dibromo-p-
xylene were purchased from Aldrich. Melting points were deter-
mined by using a Gallenkamp instrument and are given uncor-
rected. Low-resolution EI mass spectra were recorded on a
Hewlett-Packard 5988A mass spectrometer operating at 70 eV
and a direct injection probe (DIP), or by gas-chromatography on
a Hewlett-Packard 5890A chromatograph equipped with a 12 m
× 0.2 mm × 0.33 μm HP1 column. High-resolution mass spectra
were recorded on a VG Autospec spectrometer (CACTI, Univer-
1
sity of Vigo). H and 13C NMR spectra were recorded at room
temperature, either at 200 and 50.3 MHz, respectively, on a
Bruker WP 200 SY spectrometer, or at 400 and 100.6 MHz,
respectively on a Bruker ARX-400 spectrometer.
3-(Tosyloxy)benzaldehyde. A solution of NaOH (4 g,
100 mmol) in water (100 mL) containing TEBA (100 mg) was
added to one of 3-hydroxybenzaldehyde (6.1 g, 50 mmol) in
dichloromethane (100 mL) at 0 °C. The mixture was allowed to
reach room temperature, after which a solution of p-toluenesul-
phonyl chloride (11.5 g, 60 mmol) in dichloromethane (100 mL)
was added and the mixture stirred at room temperature for 12 h.
The organic layer was then washed with water and dried over
MgSO4. The solvent was removed and the residue washed with
hexane to obtain the title compound (92%) as a white solid. Mp
62–65 °C. δH (200 MHz, CDCl3): 2.43 (3H, s, –CH3), 7.28 (3H,
m, H-4, Ts), 7.46 (2H, m, H-2, H-5), 7.66 (2H, d, J = 8.1 Hz,
Ts), 7.72 (1H, d, J = 8.1 Hz, H-6), 9.87 (1H, s, –CHO). δC
(50 MHz, CDCl3): 21.7, 123.0, 128.2, 128.4, 129.9, 130.4,
2,4-Bis[3′-(hydroxyl)benzyloxy]benzophenone (4a). A solu-
tion of KOH (1.3 g, 23 mmol) in methanol (6 mL) was added to
one of 2,4-bis[3′-(tosyloxy)benzyloxy]benzophenone (1.4 g,
1.9 mmol) in methanol (17 mL) and refluxed for 3 h. Once
cooled, the mixture was filtered and concentrated.
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Dichloromethane (50 mL) was then added and the organic layer
washed with water (2 × 25 mL). The aqueous layer was neutral-
ized with 10% aqueous HCl and extracted with dichloromethane.
Organic layers were combined and dried over anhydrous
MgSO4, after which the solvent removed. Purification by column
chromatography in silica gel (95 : 5, chloroform–methanol) gave
the desired compound (71%) as a white solid. Mp 161–163 °C.
δH (400 MHz, CDCl3 + CD3OD): 4.73 (2H, s, Ar′′–CH2–O–Ar),
4.87 (2H, s, Ar′′′–CH2–O–Ar), 6.28 (1H, d, J = 7.7, H-6′′), 6.46
(3H, m, H-3, H-5, H-2′′), 6.50 (1H, d, J = 7.7, H-4′′), 6.63 (1H,
d, J = 7.7, H-4′′′), 6.73 (2H, m, H-2′′′, H-6′′′), 6.86 (1H, t, J =
7.7, H-5′′), 7.05 (1H, t, J = 7.7, H-5′′′), 7.24 (3H, m, H-6, H-3′,
H-5′), 7.36 (1H, t, J = 7.7, H-4′), 7.57 (2H, d, J = 7.7, H-2′,
H-6′). δC (100 MHz, CDCl3 + CD3OD): 69.8, 69.9, 100.5,
105.9, 113.1, 113.2, 114.0, 114.1, 114.3, 114.8, 117.5, 118.4,
121.3, 127.9, 129.1, 129.3, 129.5, 132.0, 132.1, 132.4, 137.4,
137.5, 138.6, 156.5, 156.8, 158.5, 162.5, 196.9. m/z (MS-EI):
426 (M+, 1%), 107 (100), 77 (40). HRMS m/z found: 426.1469.
Calc. for C27H22O5 (M+) 426.1467.
solvent removal, gave the desired compound (71%) as a white
solid. Mp 75–76 °C. δH (400 MHz, CDCl3): 2.42 (3H, s, –CH3),
5.03 (2H, s, Ar′′–CH2–O–Ar), 6.42 (1H, dd, J = 8.6, 2.4, H-5),
6.48 (1H, d, J = 2.4, H-3), 6.93 (1H, m, H-4′′), 7.06 (1H, br s,
H-2′′), 7.29 (4H, m, H-5′′, H-6′′, Ts), 7.49 (3H, m, H-6, H-3′,
H-5′), 7.55 (1H, m, H-4′), 7.61 (2H, d, J = 8.6, H-2′, H-6′), 7.68
(2H, d, J = 8.6, Ts). δC (50 MHz, CDCl3): 21.6, 69.1, 102.1,
107.6, 113.4, 121.1, 122.0, 125.7, 128.3, 128.4, 128.8, 129.7,
129.9, 131.5, 132.2, 135.3, 138.0, 138.1, 145.4, 149.8, 164.7,
166.1, 200.0. m/z (MS-EI): 474 (M+, 14%), 261 (56), 105 (80),
91 (100), 78 (65). HRMS m/z found: 474.1126. Calc. for
C27H22O6S (M+) 474.1137.
2-Hydroxy-4-[3′-(hydroxy)benzyloxy]benzophenone (4b). A
solution of KOH (895 mg, 16 mmol) in methanol (6 mL) was
added to one of 2-hydroxy-4-[3′-(tosyloxy)benzyloxy]benzophe-
none (1.3 g, 27 mmol) in methanol (15 mL), the reaction
mixture being stirred under reflux for 3 h. Then, the mixture was
filtered and concentrated, dichloromethane added and the
product washed with water. The aqueous layer was neutralized
with HCl (10%) and extracted with dichloromethane. The
organic layers were combined and dried, and the solvent was
removed. Purification by silica gel column chromatography
(CHCl3) followed by solvent removal, gave the desired com-
pound (73%) as a white solid. Mp 139–140 °C. δH (400 MHz,
CDCl3 + CD3OD): 5.02 (2H, s, Ar′′–CH2–O–Ar), 6.44 (1H, dd,
J = 8.6, 2.4, H-5), 6.54 (1H, d, J = 2.4, H-3), 6.76 (1H, m,
H-4′′), 6.87 (2H, m, H-2′′, H-6′′), 7.20 (1H, t, J = 8.6, H-5′′),
7.47 (4H, m, H-6, H-3′, H-4′, H-5′), 7.56 (2H, m, H-2′, H-6′). δC
(50 MHz, CDCl3 + CD3OD): 70.0, 102.0, 107.9, 113.2, 114.2,
115.2, 118.8, 128.3, 128.8, 129.8, 131.5, 135.3, 137.3, 138.1,
156.8, 165.2, 165.7, 200.1. m/z (MS-EI): 320 (M+, 9%), 107
(100), 77 (30). HRMS m/z found: 320.1046. Calc. for C20H16O4
(M+) 320.1049.
3,5,8,12-Tetraoxa-44-benzoyl-1,4,7(1,3),10(1,4)-tetrabenzena
cyclododecaphane (1). A solution of 4a (426 mg, 1 mmol) and
α,α′-dibromo-p-xylene (264 mg, 1 mmol) in anhydrous acetone
(50 mL) was added to a suspension of K2CO3 (495 mg, 5 mmol)
in anhydrous acetone (100 mL) for 7 h and then refluxed con-
tinuously for 72 h. Next, water was added to the concentrated
reaction mixture, which was neutralized with 10% aqueous HCl
and extracted with dichloromethane. The organic layer was dried
over anhydrous MgSO4 and the solvent removed. Purification by
column chromatography in silica gel (8 : 2, hexane–ethyl acetate)
gave 1 (54%) as a white solid. Mp 165–166 °C. λmax (CH3CN)/
nm: 198 (ε/mL mol−1 cm−1 9100), 246 (1300), 276 (810), 282
(800), 308 (400). δH (400 MHz, CDCl3): 4.82 (4H, s, H-2, H-6),
5.16 (2H, s, H-9), 5.20 (2H, s, H-11), 5.91 (1H, d, J = 2.1,
H-42), 6.45 (1H, dd, J = 7.8, 2.1, H-46), 6.62 (1H, s, H-72), 6.65
(1H, d, J = 7.8, H-76), 6.70 (1H, s, H-12), 6.77 (1H, d, J = 7.8,
H-16), 6.84 (1H, dd, J = 7.8, 2.1, H-74), 6.96 (1H, dd, J = 7.8,
2.1, H-14), 7.10 (1H, t, J = 7.8, H-75), 7.20 (3H, m, H-15,
H-103, H-105), 7.30 (3H, m, H-45, H-102, H-106), 7.40 (2H, t, J
= 7.8, H-3′, H-5′), 7.51 (1H, t, J = 7.8, H-4′), 7.76 (2H, d, J =
7.8, H-2′, H-6′). δC (100 MHz, CDCl3): 68.6 (C-9), 69.5 (C-2),
69.6 (C-11), 70.3 (C-6), 102.3 (C-42), 103.8 (C-46), 110.6
(C-72), 111.4 (C-12), 116.6 (C-74), 117.7 (C-14), 118.3 (C-76),
119.6 (C-16), 122.6 (C-44), 125.6 (C-103, C-105), 127.3 (C-102,
C-106), 128.1 (C-3′, C-5′), 129.5 (C-15), 129.7 (C-2′, C-6′),
130.0 (C-75), 131.7 (C-45), 132.5 (C-4′), 136.3 (C-101), 137.1
(C-104), 137.7 (C-11), 138.5 (C-71), 138.8 (C-1′), 157.9 (C-73),
158.1 (C-43), 159.1 (C-13), 161.7 (C-41), 195.9 (CO). m/z
(MS-EI): 528 (M+, 8%), 104 (100), 78 (64). HRMS m/z found:
528.1922. Calcd for C35H28O5 (M+) 528.1937.
2,5,9-Trioxa-14-benzoyl-1,4(1,3),7(1,4)-tribenzena cyclonona-
phane (2). A solution of 4b (320 mg, 1 mmol) and α,α′-
dibromo-p-xylene (264 mg, 1 mmol) in acetone (50 mL) was
very slowly added to a suspension of K2CO3 (495 mg, 5 mmol)
in acetone (100 mL) under reflux, after which refluxing was con-
tinued for 72 h. Then, the concentrated reaction mixture was sup-
plied with water and neutralized with HCl (10%) before
extraction with dichloromethane. Purification by silica gel
column chromatography (8 : 2, hexane–ethyl acetate) gave 2
(47%) as a white solid. Mp 142–143 °C. λmax (CH3CN)/nm: 196
(ε/mL mol−1 cm−1 13 600), 246 (2800), 282 (1700). δH
(400 MHz, CDCl3): 4.82 (2H, s, H-8), 4.97 (2H, s, H-3), 5.10
(2H, s, H-6), 5.64 (1H, d, J = 2.4, H-12), 6.05 (1H, br s, H-42),
6.50 (1H, dd, J = 7.9, 2.4, H-16), 6.82 (1H, d, J = 7.9, H-46),
6.96 (1H, dd, J = 7.9, 2.4, H-44), 6.99 (2H, d, J = 7.9, H-72,
H-76), 7.04 (2H, d, J = 7.9, H-73, H-75), 7.20 (1H, t, J = 7.9,
H-45), 7.26 (1H, d, J = 7.9, H-15), 7.44 (2H, t, J = 7.9, H-3′,
H-5′), 7.55 (1H, t, J = 7.9, H-4′), 7.82 (2H, d, J = 7.9, H-2′,
H-6′). δC (50 MHz, CDCl3): 69.1 (C-3), 73.2 (C-6), 74.7 (C-8),
109.9 (C-12), 110.5 (C-16), 117.4 (C-42), 119.7 (C-44), 120.7
(C-46), 125.1 (C-14), 128.1 (C-3′, C-5′), 128.4 (C-72, C-76),
129.0 (C-73, C-75), 129.5 (C-45), 129.8 (C-2′, C-6′), 131.5
(C-15), 132.7 (C-4′), 135.8 (C-74), 136.8 (C-71), 137.6 (C-41),
138.3 (C-1′), 156.9 (C-13), 157.5 (C-43), 160.3 (C-11), 195.8
2-Hydroxy-4-[3′-(tosyloxy)benzyloxy]benzophenone. A sol-
ution of 3 (1 g, 3 mmol), 2,4-dihydroxybenzophenone (642 mg,
3 mmol) and K2CO3 (1.2 g, 8.4 mmol) in acetone (20 mL) was
stirred for 24 h. Then, water (10 mL) was added to the reaction
mixture and the acetone removed. The aqueous layer was neu-
tralized with HCl 10% and extracted with dichloromethane, the
organic layer being dried and the solvent removed. Purification
by silica gel column chromatography (CH2Cl2), followed by
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(CO). m/z (MS-EI): 422 (M+, 8%), 105 (72), 104 (85), 78 (100).
HRMS m/z found: 422.1524. Calc. for C28H22O4 (M+)
422.1518.
H-15, H-3′, H-5′), 7.51 (1H, t, J = 8.0, H-4′), 7.80 (2H, d, J =
8.0, H-2′, H-6′). δC (50 MHz, CDCl3): 71.1, 76.4, 117.4, 120.5,
121.9, 122.6, 122.7, 127.9, 128.3, 129.6, 130.1, 130.2, 130.3,
132.9, 133.0, 137.6, 138.1, 138.3, 140.3, 142.1, 156.9, 159.3,
196.4, 197.2. m/z (MS-EI): 420 (M+, 2%), 105 (57), 90 (57), 77
(100), 71 (60). HRMS m/z found: 420.1369. Calc. for C28H20O4
(M+) 420.1362.
Photochemistry
Samples were irradiated in an immersion well photo-reactor
(Pyrex) equipped with a 150 W medium-pressure mercury lamp.
Acknowledgements
3,7,10-Trioxa-13-phenyl-1(2,6)-benzofurana-2,8(1,3),5(1,4)-tri-
The authors wish to acknowledge funding by Spain’s Ministerio
de Ciencia e Innovación and FEDER (Projects CTQ2007-60190
and CTQ2010-20303).
benzenacyclodecaphane (5). A solution of
1
(60 mg,
0.11 mmol) in benzene (110 mL) was irradiated under nitrogen
for 25 min, after which the solvent was concentrated to dryness,
and the residue dissolved in 2 mL of acetone with a few drops of
HCl (1 M) and stirred at room temperature for 2 h. Water was
then added and the product extracted with CH2Cl2. The organic
layer was dried over MgSO4 and concentrated to dryness. The
resulting solid was purified by chromatography (8 : 2, hexane–
AcOEt) to obtain 4 (60%) as a white solid. Mp 222–224 °C.
λmax (CH3CN)/nm: 198 (ε/mL mol−1 cm−1 131 000), 246
(29 800), 322 (25 700), 336 (23 500). δH (400 MHz, CDCl3):
5.17 (2H, s, H-9), 5.27 (2H, s, H-4), 5.35 (2H, s, H-6), 6.52
(1H, d, J = 2.3, H-16), 6.78 (1H, dd, J = 8.1, 2.3, H-15), 6.82
(1H, d, J = 8.1, H-84), 6.87 (1H, dd, J = 8.1, 2.3, H-24), 7.00
(3H, m, H-25, H-26, H-86), 7.12 (1H, s, H-82), 7.19 (1H, d, J =
8.1, H-14), 7.21 (1H, t, J = 8.1, H-85), 7.28 (m, 1H, H-22), 7.35
(m, 1H, H-4′), 7.41 (m, 6H, H-52, H-56, H-2′, H-3′, H-5′, H-6′),
7.50 (2H, d, J = 8.1, H-53, H-55). δC (100 MHz, CDCl3): 69.2,
71.2, 72.2, 97.1, 113.4, 113.9, 115.1, 116.5, 117.2, 117.3, 118.3,
120.2, 120.5, 122.8, 126.0, 127.2, 127.6, 128.8, 129.0, 129.4,
130.6, 132.1, 132.6, 136.8, 138.5, 139.4, 148.3, 153.8, 156.6,
158.2, 159.7. m/z (MS-EI): 510 (M+, 29%), 104 (100), 78 (79).
HRMS m/z found: 510.1841. Calc. for C35H26O4 (M+)
510.1831.
Notes and references
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(99 : 1, CH2Cl2–MeOH) to obtain 5 (73%) and 6 (27%).
6. White solid. Mp 188–190 °C. δH (200 MHz, CDCl3): 3.07
(1H, s), 4.73 (1H, d, J = 13.5), 4.86 (1H, d, J = 11.4), 5.06 (1H,
d, J = 13.5), 5.33 (1H, d, J = 11.4), 5.71 (1H, d, J = 2.0, H-12),
6.15 (1H, s, H-62), 6.23 (1H, s, H-2), 6.64 (1H, dd, J = 8.1, 2.0),
6.74 (1H, dd, J = 8.1, 2.0), 6.80 (1H, dd, J = 8.1, 2.0, H-14),
6.90 (2H, m, H-64, H-66), 7.01 (1H, d, J = 8.1, H-15), 7.08 (1H,
t, J = 8.1, H-65), 7.35 (3H, m, H-3′, H-4′, H-5′), 7.52 (2H, m,
H-2′, H-6′), 7.65 (1H, dd, J = 8.1, 2.0), 7.94 (1H, dd, J = 8.1,
2.0). m/z (MS-EI): 422 (M+, 17%), 107 (100), 105 (53), 78 (70),
77 (56). HRMS m/z found: 422.1534. Calc. for C28H22O4 (M+)
422.1518.
7. White solid. Mp 196–198 °C. λmax (CH3CN)/nm: 194
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(1H, d, J = 2.6, H-12), 5.97 (1H, br s, H-62), 7.08 (1H, dd, J =
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