Photocycloaddition of chalcones to yield cyclobutyl ditopic cyclophanes

Article abstract of DOI:10.1016/j.tet.2003.10.026

The intramolecular photocycloaddition of chalcones to give cyclobutanes has proved to be a fast and convenient method to shrink a cyclophane ring to a tricyclic system, in order to prepare potential ditopic receptors. X-Ray results confirm the previously indicated structure for the cyclobutanes 2a (n=1, m=1), in which the cyclization occurs by a head-to-head syn ring closure. NMR results indicate that the same process occurs for the cyclobutanes 2b (n=2, m=2) and 2c (n=1, m=3).

Full text of DOI:10.1016/j.tet.2003.10.026

Tetrahedron 59 (2003) 9971–9978
Photocycloaddition of chalcones to yield cyclobutyl
ditopic cyclophanes
b
Francesca R. Cibin,a Nicoletta Di Bello,a Giancarlo Doddi,a Vincenzo Fares,
,
,
*
*
a
Paolo Mencarellia and Elio Ullucci
,
*
a
`
Dipartimento di Chimica e CNR IMC-Sez. Meccanismi di Reazione, Universita di Roma ‘La Sapienza’, P.le Aldo Moro 5, 00185 Roma, Italy
bIstituto di Cristallografia, Sez. di Monterotondo, Area della Ricerca Roma1 del CNR, Via Salaria Km 29,300, CP 10, 00016 Monterotondo
Stazione, Italy
Received 17 August 2003; revised 18 September 2003; accepted 9 October 2003
Abstract—The intramolecular photocycloaddition of chalcones to give cyclobutanes has proved to be a fast and convenient method to shrink
a cyclophane ring to a tricyclic system, in order to prepare potential ditopic receptors. X-Ray results confirm the previously indicated
structure for the cyclobutanes 2a (n¼1, m¼1), in which the cyclization occurs by a head-to-head syn ring closure. NMR results indicate that
the same process occurs for the cyclobutanes 2b (n¼2, m¼2) and 2c (n¼1, m¼3).
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
of the three chalcones 1a–1c and the cyclobutane 2a are
also reported.
In a previous paper we showed that in chloroform solution
the chalcone 1a photocyclises intramolecularly to the cyclo-
butane 2a, by a fast and high yield process, that occurs by a
head-to-head syn ring closure (Scheme 1).1
The formation of different stereoisomers in the dimerization
of chalcones and related compounds may be dependent on
the physical state of the substrate (solid, solution, molten
state, glass)2–9 or its complexation with Lewis acids.10 The
occurrence in solution of only one type of regiochemical
(head-to-head or head-to-tail ring closure) and stereo-
chemical ring closure, has already been observed with
cyclic trans-cynnamoyl precursors, that give the formation
of a syn head-to-head truxinic type cyclobutane (Fig. 1).11,12
Since the size of the spacer could affect to some extent the
stereochemical route of these processes, herein we wish to
report on the effect that an enlargement of the spacer has on
the intramolecular photocycloaddition of the chalcones 1b
and 1c in chloroform. X-Ray results regarding the structures
Scheme 1.
Keywords: cyclophanes; enones; chalcones; carbocycles; cycloaddition; photochemistry; photocyclization.
*
Corresponding authors. Tel.: þ39-0649913077; fax: þ39-06490631 (G.D.); tel.: þ39-0690672621; fax: þ39-0690672630 (V.F.); tel.: þ39-0649913697;
fax: þ39-06490631 (P.M.); e-mail: giancarlo.doddi@uniroma1.it; vincenzo.fares@mlib.cnr.it; paolo.mencarelli@uniroma1.it
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.10.026

9972
F. R. Cibin et al. / Tetrahedron 59 (2003) 9971–9978
stereochemical behaviour of some photosensitized dimeri-
zations, occurring in solution, has been offered.16
2. Results and discussion
Figure 1.
Chalcones 1b and 1c have been synthesized according to
the route used for the synthesis of 1a (Scheme 2).†,1 These
chalcones (3.3£1023 mol dm23 in chloroform), when
exposed to sunlight, are converted to the respective
cyclobutanes 2b and 2c, with yields (chromatographated
products) of 68% (2b) and 71% (2c). Better yields are
obtained when 1b and 1c are exposed to 14 350 nm centred
lamps, in a Rayonet reactor. In this case cyclobutanes 2b
and 2c are obtained with yields of 81 and 86%, respectively.
A syn head-to-head ring closure was also observed in the
photocycloadditions of trans-cinnamoyl derivatives,
wherein the photoactive centers are linked to a phenylene
ring in ortho relationship,13 or to a [2.2]paracyclophane
system in pseudo-geminal relationship.14 In these cases a
regiospecific ring closure is undoubtedly favoured by the
structures of the precursors, that constrain the reactive
centers in close proximity; nevertheless, this behaviour may
also be observed in some photochemical ring closure
processes of acyclic precursors, carried out in solution.
For example, the cyclization of trans–trans-dibenzylidene-
acetone in benzene give only the anti head-to-head truxinic
type cyclobutane as the photodimeric product (Fig. 2).15
At variance with the experiments carried out in solution, the
exposure to sunlight for 6 days of micro-crystals of 1a–1c,
obtained by slow evaporation of chloroform solutions, did
not give any transformation of the substrates, which were
recovered unchanged. X-Ray measurements support these
findings because, in these crystals, the CvC double bonds
are not parallel, with intramolecular distances (Fig. 3(a), (b)
and (c)) that are greater than the reported limits for solid
Recently, a rationalization of the regiochemical and
5
˚
state photodimerizations (3.5–4.2 A), even though some
exceptions have been reported.17 On the other hand the
intermolecular solid phase photocyclization is also not
permitted, since the CvC distances between the nearest
˚
˚
˚
molecules are 4.1 A (1a), 5.1 A (1b) and 5.9 A (1c).
In the crystals of 1a–1c the conjugated CvO and CvC
bonds are in the s-cis conformation, with dihedral angles v
varying from 9.4 to 15.28 for 1a, from 5.6 to 11.18 for 1b,
and from 8.9 to 9.38 for 1c (for comparison, in benzyl-
ideneacetophenone v¼16.98).18 The s-cis conformation is
frequently observed in the chalcone derivatives, but some
exceptions have been reported.19 The dihedral angles of
the OvC–CAr–CAr bonds are ,298, i.e. lower than 398 as
generally observed for aromatic enones having only
hydrogen atoms in ortho positions.20
Figure 2.
After our previous work, we were able to obtain suitable
crystals to carry out X-ray crystallographic analysis of the
cyclobutane 2a by a very slow evaporation of a chloroform
solution. The results confirm unequivocally our previous
conclusions regarding the structure of this compound
(Fig. 4), obtained by NOESY measurements.1 Nevertheless,
since suitable crystals of 2b and 2c are not available to us for
X-ray analysis, we have utilized the NMR measurements to
determine their stereochemistry.
The structure of 2c was elucidated by NOESY measure-
ments. In fact, due to the short dioxyethylene spacer, this
compound presents, like the cyclobutane 2a,1 restricted
rotations of the phenylene rings directly bonded to the
cyclobutane ring. As a consequence, both the ortho protons
and carbo0n0 s 200a and 200d, and the meta protons and carbons
300b and 3 c (Fig. 5) are not chemically equivalents.
This feature enable us to distinguish the through-space
†
Erratum: Scheme 2 of Ref. 1 shows an inverted numbering of the
phenylene group bonded to the carbonyl group.
Scheme 2.

F. R. Cibin et al. / Tetrahedron 59 (2003) 9971–9978
9973
Figure 4. Two different perspective drawings of the molecular structure of
compound 2a, showing the labelling of the atoms (the upper one) and the
˚
2h–h syn conformation (the lower one). Selected bond lengths (A): C(1)–
C(2) 1.57(2), C(1)–C(22) 1.59(2), C(2)–C(21) 1.58(2), C(21)–C(22)
1.56(2).
Figure 5.
interactions of proton 200a from those of 200d. In particular,
the NOESY spectrum of 2c shows that the protons that
we have named H-200a have a through-space coupling
exclusively with the protons H-2, whereas the protons that
Figure 3. (a) A perspective view of the X-ray molecular structure of
˚
compound 1a. The intramolecular distance of 5.6 A (dashed line) is
˚
shown. Selected bond lengths (A): O(1)–C(3) 1.22(1), O(5)–C(20)
1.23(1), C(1)–C(2) 1.335(8), C(21)–C(22) 1.32(1). (b) View of the
centrosymmetric molecular structure of compound 1b, showing the
carbonylic oxygen atoms disordered on the two crystallographically non-
˚
equivalent, O(1) and O(2) positions. The intramolecular distance of 9.9 A
between the two centrosymmetrical ethylenic carbon atoms is shown
˚
(dashed line). Selected bond lengths (A): O(1)–C(1) 1.33(2), C(1)–C(2)
1.39(2), C(2)–C(3) 1.40(2), O(2)–C(3) 1.31(2). (c) X-Ray molecular
˚
structure of compound 1c. The intramolecular distance of 8.1 A
˚
(dashed line) is shown. Selected bond lengths (A): O(1)–C(3) 1.221(7),
O(7)–C(24) 1.235(6), C(1)–C(2) 1.316(7), C(1)–C(40) 1.465(8),
C(2)–C(3) 1.466(8), C(3)–C(4) 1.472(6), C(21)–C(24) 1.482(8),
C(24)–C(25) 1.474(7), C(25)–C(26) 1.327(8), C(26)–C(27) 1.445(7).
Figure 6. NOESY spectrum of 2c (detail).

9974
F. R. Cibin et al. / Tetrahedron 59 (2003) 9971–9978
Table 1. Calculated chemical shifts and coupling constants of the AA0BB0
cyclobutyl protons of 2a–2c, in acetone-d6
24
0
0
0
JBB
(Hz)
Compound
d H-1
(ppm)
d H-2
(ppm)
JAA
(Hz)
JAB
(Hz)
JAB
(Hz)
2a
2b
2c
4.56
4.57
4.52
5.22
5.19
5.21
11.4
11.0
10.6
6.5
6.4
6.5
20.7
20.8
20.9
10.1
10.0
9.8
Even though the values of these coupling constants should
only indicate that the formation of the cyclobutane system
occurs by a head-to-head coupling,22,23 the close similarity
1
of the H NMR pattern of the cyclobutyl moieties strongly
suggests that also for 2b the formation of cyclobutane ring
occurs by syn junction.
We have attempted to evaluate the differences of reactivity
of the three chalcones 1a–1c, by irradiation at 419 nm of
diluted chloroform solutions (,1026–1025 mol dm23),
kept at 258C in a quartz cell into a Rayonet reactor,25 and
monitoring the progress of the reactions by UV–vis
spectroscopy. These processes have shown the presence
of isosbestic points, that suggest the absence of appre-
ciable quantities of intermediates and/or by-products, at
least at these low concentrations, and clean first order
Figure 7. Head-to-head syn structure of 2c (the dioxyethylene chains have
been omitted).
we have named H-200d couple through the space only with
the protons H-1 (Fig. 6). These results, that are identical to
those obtained for compound 2a,1 indicate that there is a
trans relationship between protons H-1 and H-2, and a cis
relationship between the two H-1 protons, caused by a head-
to-head syn junction (Fig. 7).21
Table 2. First order kinetic constants for the intramolecular photocycliza-
tion 1!2, in chloroform at 258C
Owing to the larger dimensions of the trioxyethylene chains,
in the cyclobutane 2b we did not observe the restricted
rotations of the phenylene rings directly bonded to the
cyclobutane ring. Such restricted rotations, as stated
previously, made the related ortho and meta protons of 2a
and 2c not chemically equivalent, and were decisive in
establishing the structures by NOESY. However, the
Compound
k (s21
)
1a
1b
1c
9.6^0.4£1023
7.2^0.7£1023
6.4^0.4£1023
1
comparison of H NMR spectra of 2a, 2c and 2b gave
kinetics (Table 2). The ratios k1a/k1b/k1c¼1.5:1.12:1,
indicate a modest influence of the size of the polyoxyethyl-
ene chain.
suggestions about the stereoch0emistry of the latter com-
pound. Figure 8 shows the AA BB0 patterns of cyclobutyl
protons of 2a, 2b and 2c, and Table 1 reports the calculated
coupling constants for these systems.
3. Conclusions
X-Ray and NMR measurements confirm that the photo-
cyclization of cyclic bis-chalcones 1 to give the corre-
sponding cyclobutanes 2 is a process with a definite
regiochemistry and stereochemistry. The syn relationship
observed for the two carbonyl groups in the ditopic
cyclophanes 2 is an important feature, because it could
have implications on the potential ligand properties of these
compounds, and could be exploited to construct more
complex structures.
4. Experimental
4.1. General and instrumentation
Melting points were determined with a Bu¨chi capillary
instrument and are uncorrected. Thin-layer chromatography
(TLC) was carried out on Merck precoated 60 Kiesegel F254
silica gel plates and Merck precoated RP-18 F254S reverse
phase plates. Flash chromatography was carried out on
columns with flash silica gel 60 Merck (40–63 mm), or on
Gyan prepacked flash silica gel columns (40–63 mm,
Figure 8. 1H NMR spectra of cyclobutyl protons of 2a, 2b and 2c in
acetone-d6, at 458C.

F. R. Cibin et al. / Tetrahedron 59 (2003) 9971–9978
9975
40 mm I.D.£75 mm) by a JaiFlash chromatograph. All
reactions requiring anhydrous conditions were conducted in
flame-dried apparatus. 1H NMR and 13C NMR spectra were
measured on a Bruker AC 200 or a Bruker AC 300
spectrometer, at 258C unless otherwise specified. DEPT and
2D NMR spectra (H,H-COSY, H,C-COSY, NOESY-Phase
sensitive) were measured using standard Bruker software.
NOESY-Phase sensitive spectra in TPPI mode, were
recorded with mixing-times of 100–400 ms. IS-MS spectra
were obtained on a Perkin–Elmer SCIEX API 365 triple
quadrupole spectrometer. UV–vis spectra were carried out
on a Cary 300, at 258C. IR spectra were recorded on an
FT-IR Nicolet 510. Microanalyses were performed on a
Carlo Erba EA 1110 CHNS-O analyser. Photoreactions
were carried out in a Rayonet apparatus. X-Ray intensities
were collected on a Rigaku four-circle diffractometer
equipped with a rotating anode (Cu Ka radiation) by the
u–2u scan method. Data were corrected for Lorentz and
polarization effects and for absorption by the semiempirical
psi-scanmethod.Thestructuresweresolvedbydirectmethods
using the SIR2002 package of crystallographic programs,26
and refined by full-matrix least-squares methods with the
SHELXTL programs.27 Hydrogen atoms were included in
calculated positions and refined in riding mode.
conventional R¼0.062 and Rw¼0.077 for 3730 reflections
with F$6s(F). Goodness of fit¼2.09.
4.2.4. Crystal structure of 2a. Crystal data: C76H72O16,
M¼1241.4, crystallizes as colourless platelets; crystal
dimensions 0.5£0.4£0.1 mm, monoclinic, a¼23.026(9),
3
˚
˚
b¼11.42(1), c¼23.497(7) A, b¼96.98(3)8, V¼6132(8) A ,
space group P21/n, m(Cu Ka)¼0.77 mm21
,
Z¼4,
dcalc¼1.35 Mg m23
,
final conventional R¼0.064 and
Rw¼0.079 for 1600 reflections with F$6s(F). Goodnes of
fit¼1.74.
4.3. Materials
p-Toluenesulphonyl chloride (98%), diethyleneglycol
(99%), triethyleneglycol (99%) and tetrathyleneglycol
(99%) were purchased from Aldrich and have been used
without further purification. Dry K2CO3 was obtained by
overnight heating of analytical grade K2CO3 (Carlo Erba) at
1108C. Dry DMF was purchased from Fluka. Spectroscopy
grade chloroform (Carlo Erba) was used in the kinetic
experiments without further purification. The triethylene
glycol bis-(p-toluenesulfonate) 3b was prepared according
to literature.28 The preparation of 1,7-bis-(4-formylphenyl)-
1,4,7-trioxaheptane 4a and 1,7-bis-(4-[trans 3-(4-hydroxy-
phenyl)-3-oxo-propenyl]-phenyl)-1,4,7-trioxaheptane 5a,
was already described.1
4.2. Crystallographic data
The poor quality of the available, low diffracting crystals of
1a, 1b and 2a strongly affects their crystal structure analysis
and the geometrical results. Only for 1c, which crystallizes
as well formed prisms, diffraction data allowed to obtain a
better molecular model, and interatomic distances and
angles with low standard deviations.
4.3.1. 1,10-Bis-(4-formylphenyl)-1,4,7,10-tetraoxade-
cane (4b). A solution containing 3b (16.19 g, 35.3 mmol)
in dry DMF (50 mL) was added dropwise (ca. 1 h) to a
stirred suspension in dry DMF (50 mL) of 4-hydroxybenz-
aldehyde (9.40 g, 77 mmol) and dry K2CO3 (26 g,
188 mmol), kept under argon at 808C. The stirring was
continued at this temperature for 3.5 h. The resulting
mixture was filtered to remove K2CO3 and the solvent
removed in vacuo to yield a solid residue. The recovered
K2CO3 was dissolved in water and repeatedly extracted with
CH2Cl2 to remove traces of bis-aldehyde. The dichloro-
methane extracts and the solid residue were combined,
washed with aqueous NaOH (5%) until complete removal of
unreacted 4-hydroxybenzaldehyde, water (3£40 mL) and
dried on Na2SO4. The solvent was removed in vacuo to
yield a solid that was crystallized from MeOH affording
4b (9.32 g, 29.6 mmol, 81%, mp 77–788C); lit. (54%,
74–758C).29
Crystallographic data (excluding structure factors) for
the strucures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC 212952-212955.
4.2.1. Crystal structure of 1a. Crystal data: C38H36O8,
M¼620.7, crystallizes as pale-yellow thin prisms; crystal
dimensions 0.5£0.2£0.1 mm, triclinic, a¼11.674(9), b¼
˚
12.335(9), c¼12.628(5) A, a¼106.52(4), b¼94.88(4), g¼
3
˚
111.46(4)8, V¼1585(5) A , space group P-1, m(Cu-Ka)¼
0.74 mm21, Z¼2, dcalc¼1.30 Mg m23, final conventional
R¼0.075 and Rw¼0.090 for 2426 reflections with F$6s(F).
Goodness of fit¼2.29.
4.3.2. 1,10-Bis-(4-[trans 3-(4-hydroxyphenyl)-3-oxo-pro-
penyl]-phenyl)-1,4,7,10-tetraoxadecane (5b). The bis-
aldehyde 4b (1.32 g, 3.69 mmol) and 4-hydroxyaceto-
phenone (1.51 g, 11.1 mmol) were added to a stirred
solution of NaOH (1.34 g, 33.5 mmol) in EtOH/H2O
(8:2, 25 mL), kept at ,08C under argon atmosphere.
After the addition, the suspension was stirred at 508C for
,48 h until complete consumption of the bis-aldehyde 4b,
as established by reverse phase TLC (eluent: CH3CN/H2O
1:1 þ0.1% TFA). The mixture was cooled, carefully
acidified to pH 5.5 by HCl 6N and then iced water was
added until complete separation of a yellow powdered
solid, that was filtered and repeatedly washed with iced
water. Recrystallization from EtOH/H2O yielded the
bis-(4-hydroxychalcone) 5b as yellow solid (86%, mp
119–1208C).
4.2.2. Crystal structure of 1b. Crystal data: C21H22O5,
M¼354.5, crystallizes as low-diffracting pale-yellow
needles; crystal dimensions 0.4£0.05£ 0.02 mm, mono-
˚
clinic, a¼9.031(6), b¼11.549(9), c¼17.533(9) A, b¼
3
˚
100.20(3)8, V¼1800(2) A , space group
P
21/a,
m(Cu Ka)¼0.76 mm21, Z¼4, dcalc¼1.31 Mg m23, final
conventional R¼0.092 and Rw¼0.094 for 841 reflections
with F$4s(F). Goodness of fit¼2.26.
4.2.3. Crystal structure of 1c. Crystal data: C42H44O10·
CHCl3, M¼828.2, crystallizes as transparent colourless
prisms; crystal dimensions 1.0£0.2£0.1 mm, triclinic, a¼
˚
12.009(5), b¼20.815(3), c¼8.529(2) A, a¼98.11(2), b¼
3
˚
101.39(3), g¼97.78(3)8, V¼2039(1) A , space group P-1,
m(Cu Ka)¼2.52 mm21, Z¼2, dcalc¼1.35 Mg m23, final

9976
F. R. Cibin et al. / Tetrahedron 59 (2003) 9971–9978
1H NMR (DMSO-d6),§ d¼3.18 [bs, OH], 3.62 [s, 4H,
–O–CH2], 3.72–3.82 [m, 4H, –O–CH2], 4.10–4.20 [m,
131.31 [C-quat.], 143.65 [C-1], 160.70 [C-quat.], 162.45
[C-quat.], 188.43 [CvO].
0
0
4H, –O–CH2], 6.88 [AA XX , JH–H¼8.8 Hz, 4H, H-30],
3
0
0
00
3
6.99 [AA XX , 3JH–H¼8.8 Hz, 4H, H-3 ], 7.61 [d, JH–H
¼
UV–vis (CHCl3), lmax 336 nm, 1 5.0£104 cm21 dm3 mol21
.
15.6 Hz, 2H, H-1], 7.71 [d, 3JH–H¼15.6 Hz, 2H, H-2], 7.76
[AA0XX0, JH – H¼8.8 Hz, 4H, H-20], 8.02 [AA0XX0,
IR (CHCl3), nmax(CvO) 1656 cm21
.
3
3JH–H¼8.8 Hz, 4H, H-200].
MS (IS) m/z¼709 (MþH)þ.
13C NMR (DMSO-d6),§ d¼67.33, 68.88, 69.95 [–O–CH2],
114.85 [C-300], 115.32 [C-30], 119.61 [C-2], 127.57
[C-quat.], 129.30 [C-200], 130.54 [C-20], 131.03 [C-quat.],
142.65 [C-1], 160.34 [C-quat.], 162.04 [C-quat.], 187.04
[CvO].
Anal. calcd for C42H44O10 C 71.17, H 6.26. Found C 71.40,
H 6.16.
1
Compound 1c. H NMR (CDCl3),§ d¼3.65–3.80 [m, 8H,
–O–CH2], 3.85–4.00 [m, 8H, –O–CH2], 4.06–4.13
[m, 4H, –O–CH2], 4.13–4.20 [m, 4H, –O–CH2], 6.80
IR (CHCl3), nmax(CvO) 1673 cm21
MS (IS) m/z¼595 (MþH)þ.
.
[AA0XX0, JH – H¼8.7 Hz, 4H, H-300], 6.88 [AA0XX0,
3
3JH–H¼8.7 Hz, 4H, H-30], 7,33 [d, JH–H¼15.5 Hz, 2H,
3
0
0
H-2], 7.46 [AA XX , JH–H¼8.7 Hz, 4H, H-200], 7.73 [d,
4H, H-20].
3
0
0
3
Anal. calcd for C36H34O8 C 72.71, H 5.76. Found C 72.92,
H 5.62.
3JH–H¼15.5 Hz, 2H, H-1], 7.92 [AA XX , JH–H¼8.7 Hz,
4.3.3. General procedure for the preparation of
9,12,15,18,30,33,36,39-octaoxapentacyclo-[38.2.2.25,8
2
13C NMR (CDCl3),‡,§ d¼67.64, 67.70, 69.44, 69.96, 70.81
[–O–CH2], 114.28 [C-30], 115.36 [C-300], 119.11 [C-2],
127.80 [C-quat.], 129.88 [C-200], 130.53 [C-20], 131.25
[C-quat.], 143.66 [C-1], 160.66 [C-quat.], 162.43 [C-quat.],
188.28 [CvO].
.
19,22.226,29]-pentaconta-1(42),3,5,7,19,21,23,26,28,40,43,
45,47,49-tetradecaene-2,25-dione (1b) and 9,12,15,27,
30,33,36,39-octaoxapentacyclo-[38.2.2.25,8.216,19.223,26]-
pentaconta-1(42),3,5,7,16,18,20,23,25,40,43,45,47,49-tetra-
decaene-2,22-dione (1c). A solution containing 3b (or 3c)
(1 mmol) in dry DMF (200 mL) was added dropwise (ca.
5 h), to a stirred suspension of 5b (or 5a) (1 mmol) and dry
K2CO3 (690 mg, 1 mmol) in dry DMF (800 mL) and kept
under argon at 808C. The stirring was continued at this
temperature for ,3 days until complete consumption of 5,
as established by reverse phase TLC (CH3CN/H2O 7:3).
The resulting mixture was cooled and filtered to remove
K2CO3. The recovered K2CO3 was washed with DMF, the
organic phases were collected and solvent removed in vacuo
to yield a solid residue that was dissolved in CHCl3, washed
with water and dried on Na2SO4. The solvent was removed
in vacuo to yield a solid that was purified by flash
chromatography (CHCl3/acetone 9:1). Recrystallization
from CHCl3/MeOH yielded the cyclic bis-chalcone 1b
(55%, mp 203–2048C) or 1c (51%, mp 161–1628C) as
yellow solid.
UV–vis (CHCl3), lmax 336 nm, 1 3.9£104 cm21 dm3 mol21
.
IR (CHCl3), nmax(CvO) 1655 cm21
.
MS (IS) m/z¼709 (MþH)þ.
Anal. calcd for C42H44O10 C 71.17, H 6.26. Found C 71.42,
H 6.18.
4.3.4. General procedure for the preparation of
9,12,15,18,30,33,36,39-octaoxaheptacyclo-[38.2.2.25,8
.
2
19,22.226,29.02,25.03,24]-pentaconta-1(42),5,7,19,21,26,28,
40,43,45,47,49-dodecaene-4,23-dione (2b) and 9,12,15,27,
30,33,36,39-octaoxaheptacyclo-[38.2.2.25,8.216,19.223,26
2,22.03,21]-pentaconta-1(42),5,7,16,18,20,23,25,40,43,45,
.
0
47,49-dodecaene-4,20-dione (2c). Photoisomerization in
sunlight. A solution of 1b or 1c (0.163 mmol) in 50 mL of
chloroform, kept in a Pyrex flask, was exposed to
sunlight on a sunny day of April. The progress of the
reaction was followed by silica gel TLC (CHCl3) and
reverse phase TLC (CH3CN/H2O 8:2). The reaction was
stopped after ,2 h. The solution was evaporated and
the residue purified by flash chromatography (2b:
CHCl3/acetone 8:2, 68%; 2c: CHCl3/acetone 9:1, 71%).
Recrystallization from chloroform-methanol (2b) or
acetone (2c) gave microscopic white needles of an
analytically pure sample. (2b: mp 183–1848C; 2c: mp
203–2048C).
Compound 1b. 1H NMR (CDCl3),§ d¼3.72 and 3.76
[partially superimposed singlets, 8H, –O–CH2], 3.80–
3.90 [m, 8H,0 –O–CH2], 4.05–4.15 [m, 8H, –O–CH2],
0
6.86 [AA XX , JH–H¼8.6 Hz, 4H, H-300], 6.89 [AA0XX0,
3
3JH–H¼8.9 Hz, 4H, H-30], 7.32 [d, 3JH–H¼15.5 Hz, 2H, H-2],
0
0
0
3
3
7.48 [AA XX , JH–H¼8.6 Hz, 4H, H-2 ], 7.70 [d, JH–H
¼
15.5 Hz, 2H, H-1], 7.92 [AA0XX0, 3JH–H¼8.9 Hz, 4H, H-20].
13C NMR (CDCl3),‡,§ d¼67.46, 67.49, 69.54, 69.63, 70.94,
70.97 [–O–CH2], 114.35 [C-30], 115.02 [C-300], 119.30
[C-2], 127.80 [C-quat.], 130.03 [C-200], 130.58 [C-20],
Photoisomerization at 350 nm. A 6.44£1023 mol dm23
solution of 1b or 1c (25 mL) in chloroform, contained in a
Pyrex flask, was irradiated in a Rayonet reactor by 14 lamps
whose emission was centred at 350 nm. After ca. 30 min the
reaction appeared to be completed. The solvent was
removed and the residue purified by flash chromatography
(yield: 2b, 81%; 2c, 86%).
§
For the sake of simplicity, the atom numbers indicated in NMR spectra
are referred to those indicated in Scheme 2 (compounds 1b, 1c and 5b),
and Figure 5 (compound 2c; N.B., in the case of 2b: 200a¼200d¼200,
300b¼300c¼300).
‡
Erratum: in Ref. 1 is reported an erroneous assignment for C-30 and C-300
of 1a. The correct assignment is: 114.64 [C-30], 115.34 [C-300].

F. R. Cibin et al. / Tetrahedron 59 (2003) 9971–9978
9977
Compound 2b. H NMR (acetone-d6, 458C),§ d¼3.52 [s,
4H, –O–CH2], 3.60–3.65 [m, 4H, –O–CH2] and partially
superimposed 3.69 [s, 4H, –O–CH2], 3.75–3.85 [m, 4H,
–O–CH2], 4.05–4.25 [m, 8H, –O–CH2], 4.57 [m, 2H,
H-1],{ 5.19 [m, 2H, H-2],{ 6.67 and 6.70 [two partially
8.5 Hz, 4JH–H¼2.3 Hz, 2H, H-200a], 7.67 [AA0XX0, 3JH–H
¼
1
9.0 Hz, 4H, H-20].
13C NMR (acetone-d6),§ d¼43.66 [C-1], 46.22 [C-2], 69.02,
69.52, 70.63, 70.81 [–O–CH2], 115.23 [C-30], 116.49
[C-300b], 1160.81 [C-300c], 128.51 [C-200a], 131.32 [C-quat.],
131.42 [C-2 ], 132.03 [C-200d], 133.49 [C-quat.], 157.94
[C-quat.], 163.47 [C-quat.], 197.89 [CvO].
superimposed AA XX systems, JH–H¼8.8 Hz, 6H, H-30
0
0
3
and H-3 ], 7.03 [AA XX , JH–H¼8.8 Hz, 2H, H-200], 7.74
00
0
0
3
[AA0XX0, 3JH–H¼8.8 Hz, 4H, H-20].
13C NMR (acetone-d6, 458C),§ d¼43.39 [C-1], 47.19 [C-2)],
68.93, 69.04, 70.13, 71.77, 72.08 [–O–CH2], 114.66 [C-30],
115.66 [C-300], 130.06 [C-200], 131.12 [C-quat.], 131.38 [C-
20], 133.33 [C-quat.], 157.85 [C-quat.], 163.43 [C-quat.],
197.75 [CvO].
4.4. Kinetic measurements
A chloroform solution (0.3–1£1025 mol dm23) of 1a, 1b or
1c, kept in a quartz cell, was immersed in a pyrex vessel
filled with water maintained at 258C, and irradiated at
regular time intervals by an arrangement of six 419 nm
centred lamps, in a Rayonet reactor. The progress of the
reaction was followed by recording the UV–vis spectrum.
The spectra showed the presence of a isosbestic point (1a,
290 nm; 1b, 292 nm; 1c, 293 nm) and the regular decrease
of the absorbance of the chalcone and the increase of the
absorbance of the cyclobutane, according to a first order
process.
UV–vis (CHCl3), lmax 273 nm, 1 2.8£104 cm21 dm3 mol21
.
IR (CHCl3), nmax(CvO) 1677 cm21
.
MS (IS) m/z¼709 (MþH)þ.
Anal. calcd for C42H44O10 C 71.17, H 6.26. Found C 71.44,
H 6.14.
Compound 2c. 1H NMR (acetone-d6, 458C),§ d¼3.52–3.59
[m, 4H, –O–CH2], 3.62 [ps, 8H, –O–CH2], 3.78–3.85 [m,
4H, –O–CH2], 4.07–4.14 [m, 4H, –O–CH2], 4.16–4.22
[m, 4H, –O–CH2], 4.52 [m, 2H, H-1],{5.21 [m, 2H, H-2],{
References
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6.55 [dd, JH–H¼8.4 Hz, JH–H¼2.5 Hz, 2H, H-300c], 6.63
3
4
[dd, JH–H¼8.5 Hz, JH–H¼2.5 Hz, 2H, H-300b], 6.70 [dd,
3
4
2. Stobbe, H.; Bremer, K. J. Prakt. Chem. 1929, 123, 1–60.
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4
imposed 6.74 [AA0XX0, JH–H¼9.0 Hz, H-30], 7.18 [dd,
3
4. Wynberg, H.; Groen, M. B.; Kellogg, R. M. J. Org. Chem.
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3JH–H¼8.5 Hz, JH–H¼2.3 Hz, 2H, H-200a], 7.77 [AA0XX0,
4
3JH–H¼9.0 Hz, 4H, H-20].
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13C NMR (acetone-d6, 458C),§ d¼44.32 [C-1], 45.95 [C-2],
68.90, 69.49, 70.14, 70.83, 71.39, 71.54 [–O–CH2], 114.78
[C-30], 116.47 [C-300b], 116.78 [C-300c], 1020 8.41 [C-200a],
131.18 [C-quat.], 131.36 [C-20], 131.97 [C-2 d], 133.35 [C-
quat.], 157.98 [C-quat.], 163.59 [C-quat.], 197.80 [CvO].
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.
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.
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MS (IS) m/z¼709 (MþH)þ.
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Anal. calcd for C42H44O10 C 71.17, H 6.26. Found C 71.45,
H 6.16.
13. Akabori, S.; Habata, Y.; Nakazawa, M.; Yamada, Y.; Shindo,
Y.; Sugimura, T.; Sato, S. Bull. Chem. Soc. Jpn. 1987, 60,
3453–3455.
The 1H NMR and 13C NMR spectra of 2a in acetone-d6 are
reported here for comparison.
14. Zitt, H.; Dix, I.; Hopf, H.; Jones, P. G. Eur. J. Org. Chem.
2002, 2298–2307.
Compound 2a. 1H NMR (acetone-d6, 458C),§ d¼3.52–3.59
[m, 4H, –O–CH2], 3.75–3.85 [m, 4H, –O–CH2], 4.15–
4.25 [m, 4H, –O–CH2], 4.25–4.35 [m, 4H, –O–CH2], 4.56
[m, 2H, H-1],{5.22 [m, 2H, H-2],{ 6.55 [dd, 3JH–H¼8.4 Hz,
15. Shoppee, C. W.; Wang, Y.-S.; Sternhell, S.; Brophy, G. C.
J. Chem. Soc., Perkin Trans. 1 1976, 1880–1886.
16. D’Auria, M.; Emanuele, L.; Esposito, V.; Racioppi, R.
ARKIVOC 2002, XI, 65–77, http://www.arkat-usa.org/ark/
journal/2002/Spinelli/MS-575H/575H.pdf
4JH – H¼2.5 Hz, 2H, H-300c], 6.62 [dd, JH – H¼8.5 Hz,
3
4JH – H¼2.5 Hz, 2H, H-300b], 6.69 [AA0XX0, JH – H
¼
3
17. Nakanishi, H.; Hasegawa, M.; Mori, T. Acta Crystallogr.,
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19. Gawronski, J. Conformations, Chiroptical and Related
Spectral Properties of Enones. In The Chemistry of Enones;
9.0 Hz, H-30] and partially superimposed 6.71 [dd,
00
4
3
3JH–H¼8.5 Hz, JH–H¼2.5 Hz, H-2 d], 7.17 [dd, JH–H
¼
{
The estimated J values for this AA0BB0 scheme are reported in Table 1.

9978
F. R. Cibin et al. / Tetrahedron 59 (2003) 9971–9978
Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, 1989; pp
81–85.
AA0BB0 system by MestRe-C 2.3 program, Departamento de
´
´
Quımica Organica, Universidade de Santiago de Compostela-
1706 Santiago de Compostela, SPAIN: http://www.mestrec.
com/
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Chichester, 1989; pp 35–36.
25. At this wavelength the absorbances of the chalcones 1a–1c are
almost negligible and the reactions are sufficiently slow to be
followed by the used procedure. For irradiation at 350 nm the
substrates are completely transformed into products in less
than 5 s.
21. At variance with 2a, the NOESY studies of 2c have been
carried out in acetone-d6/CDCl3 solutions (2.5:1, 458C), rather
than in pure CDCl3, because in this solvent 2c seems to form
aggregates, as suggested by the presence in the 1H NMR
spectra of a downfield shift of the signal of water and of broad
signals for all the protons, that result in spin diffusion in the
NOESY spectra (in pure acetone-d6 the solubility of 2c is too
low for reliable 2D NMR experiments).
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Giacovazzo, C.; Polidori, G.; Spagna, R. J. Appl. Crystallogr.
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