Synthesis of new furan polycycles via photochemical reaction in neutral and acidic medium

Article abstract of DOI:10.1016/j.molstruc.2019.06.103

New furan derivatives of o-divinylbenzenes were synthesized and their photochemical reactivity has been investigated in neutral and acidic medium. Depending of the structure of the starting materials and pH value, the new cyclization (11, 16, 20), cycloaddiotion (12, 13, endo-17, exo-18), electrocyclization (21, 22) and dimeric (15, 19) products were isolated. While photochemical investigation in neutral medium showed that the main intramolecular process is cycloaddition, in the case of acidic photochemistry, due to the protonation of the starting molecule, electrocyclization process comes to expression and formation of dihydronaphtalene products 21 and 22.

Full text of DOI:10.1016/j.molstruc.2019.06.103

Accepted Manuscript
Synthesis of new furan polycycles via photochemical reaction in neutral and acidic
medium
Željka Kuzmić, Irena Škorić, Željko Marinić, Dragana Vuk
PII:
S0022-2860(19)30826-9
DOI:
https://doi.org/10.1016/j.molstruc.2019.06.103
MOLSTR 26745
Reference:
To appear in: Journal of Molecular Structure
Received Date: 17 May 2019
Revised Date: 18 June 2019
Accepted Date: 28 June 2019
Please cite this article as: Ž. Kuzmić, I. Škorić, Ž. Marinić, D. Vuk, Synthesis of new furan polycycles via
photochemical reaction in neutral and acidic medium, Journal of Molecular Structure (2019), doi: https://
doi.org/10.1016/j.molstruc.2019.06.103.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical abstract
Synthesis of new furan polycycles via photochemical reaction in neutral and acidic
medium

ACCEPTED MANUSCRIPT
Synthesis of new furan polycycles via photochemical reaction in neutral and acidic
medium
Željka Kuzmića,•, Irena Škorića, Željko Marinićb and Dragana Vuka,
aDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb,
Marulićev trg 19, 10000 Zagreb, Croatia,
bNMR Centre, Ruđer Bošković Institute, Bijenička cesta 54, 10001 Zagreb, Croatia
Abstract
New furan derivatives of o-divinylbenzenes were synthesized and their photochemical
reactivity has been investigated in neutral and acidic medium. Depending of the structure of
the starting materials and pH value, the new cyclization (11, 16, 20), cycloaddiotion (12, 13,
endo-17, exo-18), electrocyclization (21, 22) and dimeric (15, 19) products were isolated.
While photochemical investigation in neutral medium showed that the main intramolecular
process is cycloaddition, in the case of acidic photochemistry, due to the protonation of the
starting molecule, electrocyclization process comes to expression and formation of
dihydronaphtalene products 21 and 22.
Keywords: Furan, Photochemistry, Electrocyclization, Cycloaddition, Protonation
•Present name and adress: Željka Kuzmić Čorak, Quality Control, Immunobiological laboratory, GENERA d.d., Svetonedeljska 2,
Kalinovica, 10436 Rakov Potok, Croatia
Corresponding author. Tel.: +385 1 4597 246; fax: +385 1 497 250; e-mail: dvuk@fkit.hr (D. Vuk)
1

ACCEPTED MANUSCRIPT
Introduction
The photochemistry of stilbene-like [1-3] compounds was the subject of intensive research
over the past years [4-17] while it was considered as a convenient way for photochemical
synthesis of complex polycyclic structures whose synthesis has been hampered by a classical
procedure. Of particular interest in this field are annulated heterocyclic derivatives of o-
divinylbenzenes [12-17] which could produce a number of new interesting compounds,
depending on structure of starting material and experimental conditions. In few of our
previous papers [12-15], photoreactivity of annulated difuran and dithiophene derivatives was
thoroughly explored and mutually compared. While difuryl derivatives [14] upon irradiation
mostly gave intramolecular products of cycloaddition reaction, in the case of dithienyl
derivatives [12] the main photochemical process is electrocyclization process, depending on
the position of the sulphur in the aromatic moiety.
R
S
R
R
R
R
O
O
O
S
S
S
S
S
R
1a-b
O
3a-c
4a-c
5a-c
2a-b
R = H, CH3, Br
R
R
S
S
S
S
S
S
S
R
S
R
S
9a-b
S
8a-b
6a-c
10a-b
7a-c
Figure 1.
Further, in one of our previous paper, we studied the photochemical behavior of dithienyl
derivatives in acidic medium and showed that the photoreactivity could be completely
changed upon different pH value [13]. While the main isolated photoproduct in neutral
medium was dihydronaphtalene derivative 3a-c, photochemistry in acidic medium towards the
reaction course to the other direction and formation of compounds 5a-c, 6a-c and 7a-c. On the
other side, except the pH value, we showed that the position of heteroatom in the aromatic
moiety may also affect to the photochemical reactivity of starting material, whereby the new
complex polycyclic systems 10a-b were obtained.
As a continuation of the previous study, the aim of this work is to explore the influence of
type of heteroatom in the aromatic moiety to the reaction mechanism, which could bring the
useful information from the synthetic point of view. For this purpose the novel annulated furyl
2

ACCEPTED MANUSCRIPT
derivatives with different position of oxygen in furan were prepared and their photoreactivity
was investigated in neutral and acidic medium.
Results and Discussion
The synthesis of 2-[(E)-2-{2-[(E)-2-(furan-2-yl)ethenyl]phenyl}ethenyl]furan (1a) and 2-[(E)-
2-{2-[(E)-2-(1-benzofuran-2-yl)ethenyl]phenyl}ethenyl]-1-benzofuran (1b) have been
previously reported [11]. The novel compounds 1c-d were prepared by analogue procedure
[14] from β,β-o-xylyl(ditriphenylphosphonium)dibromide and the corresponding aldehydes
(Scheme 1). The products are obtained in very good yields (75-90 %) as mixtures of cis,cis-,
cis,trans- and trans,trans-isomers.
Scheme 1.
After repeated column chromatography the isomers of 3-[2-{2-[2-(furan-3-
yl)ethenyl]phenyl}ethenyl]furan (1d) were isolated and completely characterized, while in the
case of 2-methyl-5-[2-{2-[2-(5-methylfuran-2-yl)ethenyl]phenyl}ethenyl]furan (1c), only
trans,trans-isomer was isolated as it was obtained as the major product in the reaction
1
mixture. Compared H NMR spectra of cis,cis-, cis,trans- and trans,trans-isomers 1d are
shown on Figure 2. Ethylenic protons in all cases appear as dublets between 6.30 and 7.10
ppm, with shift to higher field of trans-ethylenic protons in accordance with its increased
molecular planarity.
O
O
trans,trans-1d
PPM
7.4
7.2
7.0
6.8
6.6
6.4
Figure 2.
3

ACCEPTED MANUSCRIPT
UV spectra for isomers of compound 1d (Figure 3) show expected red shift of trans,trans-1d
with hyperchromic effect in regards to the cis,cis-isomer.
20000
cis,cis-1d
cis,trans-1d
trans,trans-1d
18000
16000
14000
12000
10000
8000
6000
4000
2000
250
300
350
λ
/ nm
Figure 3.
Photochemistry in neutral media
Prepared compounds 1c-d were subjected to irradiation in neutral medium, while the
irradiation experiments in acidic medium were performed for all the compounds 1a-d.
Irradiation in neutral medium were performed by the previously described procedure for the
compounds 1a-b [14]. The mixture of isomers of starting compounds 1c-d were irradiated in
toluene under anaerobic conditions in Rayonet reactor at 350 nm during 16 h. After
evaporation of the solvent the crude reaction mixture was chromatographed with petroleum
ether as eluent. The mixture obtained from irradiation of dimethyl derivative 1c gave two
novel products, the phenanthrene derivative 11 and the furo-benzobicyclo[3.2.1]octadiene
compound exo-12 (Scheme 2). In the case of 3-furyl derivative 1d the polycyclic compound
13 was the only isolated photoproduct (Scheme 3).
Scheme 2.
4

ACCEPTED MANUSCRIPT
Scheme 3.
Scheme 4. shows assumed mechanism of formation of photoproducts 11 and exo-12.
Cyclization derivative 11 formed by 10π electrocyclization process and subsequent
elimination of water, while the furo-benzobyciclo[3.2.1]octadiene compound 12 was
generated via the well studied cycloaddition reaction of 1b followed by 1,6-ring closure and
hydrogen shift.
Scheme 4.
Photochemistry in acidic media
Photochemical experiment in acidic media were performed by irradiation of starting
compounds 1a-d in acetonitrile solution in the presence of hydrochloric acid in anaerobic
conditions for 2 h. After treatment, the reaction mixture was chromatographed by the column
chromatography, by which all formed products were isolated, respectively.
Analysis of the photochemical results of the unsubstituted derivative 1a gave three products:
molecule of phenanthrene 14 (6 %), furo-benzobicyclo[3.2.1]octadiene derivative exo-2a
5

ACCEPTED MANUSCRIPT
(6%) and dimeric product 15 (2%), which were also obtained by irradiation of the same
compound in neutral medium [14]. The indane/indene derivatives which were formed by
acidic irradiation of the analogue thiophene derivative [13] in this case were not found.
Scheme 5.
The irradiation of benzofuro-derivative 1b led to similar results. In the first fraction the
cyclisation compoud 16 (15%) was isolated, followed by benzobicyclo[3.2.1]octadiene
photoproducts exo-2b (20%), endo-17 (2%), exo-18 (20%) and dimeric product 19 (15%).
While the bicyclo[3.2.1]octadiene exo-2b and dimer 19 were obtained in the neutral medium,
the photoproducts 16-18 were the new compounds isolated only in the acidic medium.
Formation of bicyclic derivatives endo-17 and exo-18 may put in the correlation with the
previous results obtained on photochemical investigation of difuran derivatives 1a and 1b in
neutral medium. As a main intramolecular product bicyclo[3.2.1]octadiene compound of exo
orientation was obtained, while the endo derivative found only in traces or was not observed,
respectively. The similar proportion of isomers was noticed in the case of endo-17 and exo-
18. The product exo-18 was isolated as the main photoproduct, while derivative endo-17 was
obsereved as a minor product. The assumption is that the products endo-17 and exo-18 were
formed probably by opening of furan ring in acidic medium of bicyclic derivatives exo-2b and
endo-2b, respectively. Larger ratio of exo compound was explained by formation of sterically
more favorable intermediate A1 due to preferred trans ring closure (Scheme 7).
6

ACCEPTED MANUSCRIPT
Scheme 6.
Scheme 7.
7

ACCEPTED MANUSCRIPT
Structures of the new compounds endo-17 and exo-18 are completely characterized and
1
confirmed by spectroscopic techniques. Figure 4. shows the aliphatic region of H NMR
spectra of new bicyclic derivatives endo-17 and exo-18, compared with the known compound
exo-2b. Six-proton pattern between 3.2 and 4.8 ppm in the case of endo-17 and exo-18 clearly
indicates the opening of the furan ring. Proton A in both cases appears with similar shifts as
triplet or doublet of doublets, due to the coupling with protons E and F. It is interesting that
proton A couples with the both endo and exo-oriented proton E, respectively, unlike the
bicyclic compound 2b, where only the couple with exo-oriented proton was visible.
HA
HE
HD
HB
HC
O
HC, HD
HA
HE
HB
HE/F
HE/F
HB
HA
HC
HF
O
HD
endo-17
HE/F
HC/D
HE/F
HB
HA
HC/D
PPM
4.6
4.4
4.2
4.0
3.8
3.6
3.4
3.2
3.0
Figure 4.
Further, photochemical investigation in acidic medium has been expanded to the dimethyl
derivative 1c showing completely different photoreactivity (Scheme 8). Under 6π
electrocyclization process photoproduct 11 (16 %) was formed, which through additional
cyclization reaction led to the photoproduct 20 (11%). Unlike previous cases, where
cycloaddition reaction and formation of bicyclic skeleton preceded, in this case as a main
photoproduct dihydronaphtalene derivative 21 (17%) was isolated.
Scheme 8.
8

ACCEPTED MANUSCRIPT
The assumed mechanism of formation of product 21 is shown on scheme 9. Polarization of
the starting molecule (A, A') in the excited state [18] enables an easier protonation which lead
to intermediate B. Subsequently 1,9-H shift of intermediate B give carbocation B' which
undergoes 1,6-ring closure to intermediate C and by deprotonation process gives the final
photoproduct. The intermediate C could be formed also by protonation of the
dihydronaphthalene intermediate DI and 1,5-H shift.
Scheme 9.
It is interesting that 3-furyl derivative 1d in acidic medium behaves very similar, whereby the
dihydronaphtalene compound 22 was isolated as the only photoproduct (Scheme 10). The
1
aliphatic part of H NMR spectra of 21 and 22 present classical three-proton pattern of ABX
systems, with a slight shift of signals to the lower field in the case of compound 22.
Scheme 10.
9

ACCEPTED MANUSCRIPT
HB
HX
HA
HB
HX
HA
PPM
4.4
4.2
4.0
3.8
3.6
3.4
3.2
3.0
Figure 5.
Further, these results could be compared with analogue photochemical investigation on
thiophene derivatives [13]. In the case of three substituted heteroaromatic moiety similar
results were obtained regardless of the type of heteroatom. In both cases the polycyclic
product (in neutral) and dihydronaphtalene derivative (in acidic) were isolated, respectively.
On the other hand, the position 2 of heteroatom in aromatic moiety leads us in the opposite
direction. Due to the greater influence of heteroatom on electronic properties of starting
molecule, completely different type of products were obtained with the change of heteroatom
in the molecule. Thus, as the 2-substituted thiophene derivatives of o-divinylbenzene prefers
electrocyclization process in neutral and acidic medium, the presence of furyl moiety leads to
cycloaddion products, with some cyclization and dimeric derivatives, whereby the type and
share of photoproducts depends of annelation of the starting material and pH value. The
cyclization reaction in the presence of iodine has also been carried out on all starting
compounds 1a-d, whereby similar cyclization products were not observed.
Conclusion
Through this paper we showed how slightly change of structure can have a significant impact
on the reaction mechanism and distribution of products. By changing the type of heteroatom,
its position in the heteroaromatic ring and experimental conditions (time of reaction,
concentration and pH value) it could be obtained a set of completely different compounds.
While in neutral medium the cycloaddition reaction is the predominant intramolecular
process, in acidic medium, due to the protonation of the starting material other processes
appears and towards the reaction course in a different direction. In this way, by choosing the
photochemical conditions it is possible to obtain by simple synthetic procedure the complex
polycyclic structures, whose skeleton is often found in numerous natural biologically active
molecules [19-22]. Since their isolation from the plants, as well as their synthesis, often could
be found with some difficulties, there is an increasing need for such simple and environmental
friendly controlled synthesis.
4. Experimental section
10

ACCEPTED MANUSCRIPT
4.1. General experimental information
The 1H spectra were recorded on a spectrometer at 300 and 600 MHz. The 13C NMR spectra
were registered at 150 MHz. All NMR spectra were measured in CDCl3 using
tetramethylsilane as reference. The assignment of the signals is based on 2D-CH correlation
and 2D-HH-COSY experiments. UV spectra were measured on an UV/VIS Cary 50
spectrophotometer. IR spectra were recorded on an FTIR-ATR (film). Mass spectra were
obtained on a GC-MS system. Irradiation experiments were performed in a quartz vessel in
toluene solution in a photochemical reactor equipped with 3500 Å lamps. All irradiation
experiments were carried out in deaerated solutions by bubbling a stream of argon prior to
irradiation. Melting points were obtained using microscope equipped apparatus and are
uncorrected. HRMS analysis were carried out on a mass spectrometer (MALDI TOF/TOF
analyser), equipped with Nd:YAG laser operating at 355 nm with firing rate 200 Hz in the
positive (H+) or negative (H-) ion reflector mode. Silica gel (0.063e0.2 mm) was used for
chromatographic purifications. Thin-layer chromatography (TLC) was performed silica gel 60
F254 plates. Solvents were purified by distillation.
4.2. General method for the synthesis of starting compounds 1a-d
To a stirred solution of the triphenylphosphonium salt (0.005 mol) and the corresponding
aldehyde (0.011 mol) in absolute ethanol (100 mL) the solution of sodium ethoxide (0.253 g,
0.011 mol in 15 mL of absolute ethanol) was added dropwise. The reaction was complete
within 3 - 4 h (usually was left to stand overnight). After removal of the solvent, the residue
was worked up with water and benzene. The benzene extracts were dried (anhydrous MgSO4)
and concentrated. The crude reaction mixture was purified and the isomers of products and
were separated by repeated column chromatography on silica gel using petroleum ether as the
eluent. The first fractions yielded cis,cis-, cis,trans- and the last fractions trans,trans-isomers.
All isomers of 3-[(E)-2-{2-[(E)-2-(furan-3-yl)ethenyl]phenyl}ethenyl]furan (1d) are separated
and described by spectroscopic methods whereas in the case of 1c only trans,trans-isomer is
isolated. Compunds 1a-b are described previously [14].
2-methyl-5-[(E)-2-{2-[(E)-2-(5-methylfuran-2-yl)ethenyl]phenyl}ethenyl]furan (1c). Yield
1
95%; according to H NMR spectra a mixture of 10% cis,cis-1c, 50% cis,trans-1c and 40%
11

ACCEPTED MANUSCRIPT
trans,trans-1c. Compound trans,trans-1c: Rf 0.42 (petroleum ether / dichloromethane = 9:1);
yellow crystals; mp 60 - 65 ºC; UV (EtOH) λmax (ε) 298 (9069); 1H NMR (CDCl3, 600 MHz)
δ 7.48 – 7.52 (m, 2H, H-ar), 7.32 (d, J = 16.1 Hz, 2H, H-et), 7.19 - 7.23 (m, 2H, H-ar), 6.73
(d, J = 16.1 Hz, 2H, H-et), 6.25 (d, J = 3.3 Hz, 2H, H-4f), 6.02 (d, J = 3.3 Hz, 2H, H-3f), 2.37
(s, 3H, H-CH3); 13C NMR (CDCl3, 600 MHz) δ 151.9 (s), 151.5 (s), 150.8 (s), 150.2 (s), 135.3
(s), 126.8 (d), 125.6 (d), 122.7 (d), 118.4 (d), 109.5 (d), 107.3 (d), 13.3 (q); IR 2160, 1977,
1719, 763 cm-1; HRMS: M+calcd 291.1385; M+found 291.1393.
3-[(E)-2-{2-[(E)-2-(furan-3-yl)ethenyl]phenyl}ethenyl]furan (1d). Yield (75%); according
1
to H NMR spectra a mixture of 15% cis,cis-1d, 15% cis,trans-1d and 45% trans,trans-1d.
Compound cis,cis-1d: Rf 0.85 (petroleum ether / dichloromethane = 9:1); colourless oil; UV
1
(EtOH) λmax (ε) 274 (8253); H NMR (CDCl3, 600 MHz) δ 7.36 (dd, J = 8.8 Hz, 1H, H-ar),
7.28 (s, J = 5.7 Hz, 1H, H-f), 7.23 (dd, J = 8.8 Hz, 1H, H-ar), 7.18 (t, J = 1.8 Hz, 1H, H-f),
6.48 (d, J = 12.3 Hz, 1H, H-et), 6.38 (d, J = 12.3 Hz, 1H, H-et), 5.95 (d, J = 1.77 Hz, 1H, H-
13
f); C NMR (CDCl3, 600 MHz) δ 142.0 (d), 141.6 (d), 140.8 (s), 136.5 (s), 128.8 (d), 128.6
(d), 126.7 (d), 119.9 (d), 109.6 (d).
Compound cis,trans-1d: Rf 0.81 (petroleum ether / dichloromethane = 9:1); colourless oil; UV
1
(EtOH) λmax (ε) 286 (11337); H NMR (CDCl3, 600 MHz) δ 7.62 (d, J = 7.8 Hz, 1H, H-ar),
7.49 (s, 1H, H-f), 7.37 (t, J = 1.5 Hz, 1H, H-f), 7.24-7.30 (m, 3H, H-ar, H-f), 7.19 (td, J = 7.5;
1.5 Hz, 1H, H-ar), 7.15 (t, J = 1.5 Hz, 1H, H-f), 6.98 (d, J = 16.2 Hz, 1H, H-et), 6.89 (d, J =
16.2 Hz, 1H, H-et), 6.61 (d, J = 11,8 Hz, 1H, H-et), 6.58 (d, J = 1.7 Hz, 1H, H-f), 6.52 (d, J =
13
11.8 Hz, 1H, H-et). 5.92 (d, J = 1.7 Hz, 1H, H-f); C NMR (CDCl3, 600 MHz) δ 143.1 (d),
142.0 (d), 141.7 (d), 140.4 (d), 136.2 (s), 135.1 (s), 129.2 (d), 127.4 (d), 127.1 (d), 126.6 (d),
125.9 (d), 124.5 (d), 124.3 (s), 122.0 (s), 120.8 (d), 119.1 (d), 109.6 (d), 107.0 (d).
Compound trans,trans-1d: due to the similar chromatographic properties with antother two
isomers it was not possible to obtain a sufficient amount of pure trans,trans-1d for 13C NMR;
Rf 0.76 (petroleum ether / dichloromethane = 9:1); colourless oil; UV (EtOH) λmax (ε) 243
(6239), 285 (19376); 1H NMR (CDCl3, 600 MHz) δ 7.55 (s, 1H, H-f), 7.52 (d, J = 7.5 Hz, 1H,
H-ar), 7.44 (t, J = 1.3 Hz, 1H, H-f), 7.24-7.27 ( m, 1H, H-ar), 7.14 (d, J = 16.1 Hz, 1H, H-et),
6.86 (d, J = 16.1 Hz, 1H, H-et), 6.69 (d, J = 1.3 Hz, 1H, H-f); IR 2160, 1752, 1655 cm-1;
HRMS: M+calcd 263.1072; M+found 263.1082.
4.3. Irradiation experiments of 1c-d in neutral medium
12

ACCEPTED MANUSCRIPT
A mixture of cis,cis-, cis,trans- and trans,trans-isomers of 1c-d in toluene (3.4x10-4 M) was
purged with argon for 30 min and irradiated at 350 nm in a Rayonet reactor (16 lamps) in a
quartz vessel for 21 h. After irradiation the solvent was removed in vacuo and the oily residue
chromatographed on a silica gel column using petroleum ether as the eluent. The
photoproduct 11 was isolated from the enriched first chromatographic fractions followed by
compund 12. In the case of 1d the product 13 was the only isolated product. High-molecular-
weight products remained on the column.
2-methyl-5-(3-methylphenanthren-4-yl)furan (11): Rf 0.45 (petroleum ether
/
dichloromethane = 9:1); colourless crystals; mp 55 - 60 ºC; UV (EtOH) λmax (ε) 354 (1406),
1
337 (1640), 299 (8531), 287 (9181), 268 (14892, sh), 251 (26129); H NMR (CDCl3, 600
MHz) δ 7.83 (d, JA,B = 8.0 Hz, 1H, H-B), 7.80 (d, JD,E = 7.8 Hz, 1H, H-E), 7.67 (dd, JD,E
=
7.8; JC,D = 13.3 Hz, 2H, H-D, H-C), 7.5 (d, JA,B = 8.0 Hz, 1H, H-A), 7.44-7.48 (m, 1H, H-F),
13
7.25-7.29 (m, 1H, H-G), 7.24 (1H, H-H), 2.44 (s, 3H, -CH3), 2.39 (s, 3H, -CH3); C NMR
(CDCl3, 150 MHz) δ 138.3 (s); 133.1 (s); 131.2 (s); 130.3 (s); 129.9 (s); 129.3 (d); 128.9 (s),
128.1 (d); 127.8 (d); 127.1 (s); 126.5 (d); 126.4 (d); 126.2 (d); 125.5 (d); 125.0 (d); 113.5 (s);
109.4 (d); 106.9 (d), 18.7 (q), 13.6 (q). IR 2160, 1831, 1685, 1449, 744 cm-1; HRMS: M+
calcd
273.1279; M+found 273.1282.
4-methyl-15-(5-methylfuran-2-yl)-5-oxatetracyclo[6.6.1.0²,⁶.0⁹,¹⁴]pentadeca-
2(6),3,9,11,13-pentaene (12): Rf 0.12 (petroleum ether / dichloromethane = 9:1); colourless
1
oil; UV (EtOH) λmax (ε) 278 (1588), 270 (1701), 229 (17183, sh); H NMR (CDCl3, 600
MHz) δ 7.28 (d, J = 7.08 Hz, 1H, H-ar), 7.01-7.08 (m, 3H, H-ar), 5.85 (d, J = 0.7 Hz, 1H),
5.67 (dd, J = 1.3 Hz, 1H), 5.49 (d, J = 3.0 Hz, 1H), 3.92 (s, 1H, H-A), 3.71-3.75 (m, 1H, H-
B), 3.52 (s, 1H, H-E), 3.22 (dd, J = 4.97; 16.0 Hz, 1H, H-C), 2.68 (d, JC,D = 16.0 Hz, 1H, H-
13
D), 2.19 (s, 3H, -CH3), 2.17 (s, 3H, -CH3); C NMR (CDCl3, 150 MHz) δ 154.9 (s), 150.1
(s), 149,8 (s), 149.7 (s), 144.1 (s), 142.5 (s), 126.2 (d), 125.8 (d), 124.9 (s), 124.0 (d), 120.6
(d), 105.3 (q), 105.1 (q), 103.8 (d), 52.3 (d), 44.8 (d), 43.6 (d), 31.0 (t), 13.1 (q), 13.0 (q). IR
2160, 1977, 1735, 763 cm-1; HRMS: M+calcd 291.1385; M+found 291.1373.
13

ACCEPTED MANUSCRIPT
15-(furan-3-yl)-11-oxapentacyclo[7.5.1.0²,¹⁴.0³,⁸.0¹⁰,¹⁴]pentadeca-3,5,7,12-tetraene (13):
Rf 0.62 (petroleum ether / dichloromethane = 9:1); colourless oil; UV (EtOH) λmax (ε) 229
(5922), 214 (10905);1H NMR (CDCl3; 600 MHz) δ 7.25 (d, J = 7.5 Hz, 1H, H-ar), 7.17 (td, J
= 7.5 Hz, 1H, H-ar), 7.07 (t, J = 1.5 Hz, 1H, H-f), 7.04 (td, J = 7.5 Hz, 1H, H-ar), 6.88 (d, J =
7.5 Hz, 1H, H-ar), 6.76 (d, J = 0.7 Hz, 1H, H-f), 6.59 (d, J = 2.85 Hz, 1H, H-f), 5.61 (d, J =
0.7 Hz, 1H, H-f), 5.32 (d, J = 2.85 Hz, 1H, H-f), 4.18 (s, 1H, H-B), 3.92 (dd, J = 7.1; 3.2 Hz,
1H, H-A), 3.59 (d, J =4.1 Hz, 1H, H-C), 2.9 (d, J = 7.2 Hz, 1H, H-D), 1.61 (dd, J = 7.2; 3.2
Hz, 1H, H-E); 13C NMR (CDCl3, 150 MHz) δ 149.3 (d), 135.0 (s), 134.8 (s), 134.7 (s), 126.7
(d), 126.3 (d), 125.4 (d), 125.0 (d), 122.9 (s), 109.9 (d), 103.5 (d), 92.3 (d), 48.0 (d), 33.4 (d),
31.1 (d), 29.2 (d), 29.1 (d), 26.7 (d). IR 2160, 1701, 1685 cm-1; HRMS: M+
M+found 263.1071.
263.1072;
calcd
4.4. Irradiation experiments of 1a-d in acidic medium
A mixture of cis,cis-, cis,trans- and trans,trans-isomers of 1a-d in acetonitrile (4 × 10-3 M),
with addition of hydrochloric acid (36 %, 0.5 ml, 17 eq), was purged with argon for 30 min
and irradiated at 350 nm in a Rayonet reactor (16 lamps) in a quartz vessel for 2 h. After
irradiation the reaction mixture was neutralized with solution of sodium hydroxide (10 %) and
extracted with ethylacetate (4 × 5 ml). After drying over magnezium sulphate the solvents
were removed in vacuo and the oily residue chromatographed on a silica gel column using
petroleum ether as the eluent. The obtained mixtures of the products were rechromatographed
and after the repeated column chromatography different new photoproducts were isolated
from 1a-d. High-molecular-weight products remained on the column. The data for the
synthesized and isolated compounds are given below.
14

ACCEPTED MANUSCRIPT
11-exo-2-furyl-9,10-dihydro-4,9-methano-4H-benzo[4,5]cyclohepta[1,2-b]furan (exo-2a)
[14]: Yield 6.0 %, colourless crystals, m.p. 104-105 ºC; Rf = 0.42 (petroleum ether/CH2Cl2
1
4:1); UV (EtOH): λmax (ε) 267 (4365), 222 nm (10965); H NMR (600 MHz, CDCl3) δ 7.30
(d, J = 6.9 Hz, 1H; H(ar)), 7.24 (d, J = 1.8 Hz, 1H; H-5), 7.16 (d, J ~ 1 Hz, 1H; H-5'), 7.11-
7.03 (m, 3H; H(ar)), 6.29 (d, J = 1.8 Hz, 1H; H-4), 6.12 (dd, J = ~ 1, 3.3 Hz, 1H; H-4'), 5.65
(d, J = 3.3 Hz, 1H; H-3’), 4.04 (s, 1H; H-A), 3.81 (d, J = 4.8 Hz, 1H; H-B), 3.59 (s, 1H; H-E),
13
3.26 (dd, J = 4.8, 16.2 Hz, 1H; H-C), 2.74 (d, J = 16.2 Hz, 1H; H-D); C NMR (CDCl3) δ
156.8 (s), 150.1 (s), 146.6 (s), 142.5 (s), 140.8, 140.6 (2d), 126.7 (d), 126.4 (d), 124.4 (s),
121.2 (d), 109.9 (d), 108.1 (d), 104.9 (d), 52.6 (d; C-B), 45.0 (d; C-C), 44.0 (d; C-A), 31.4 (t;
C-DE), 1 signal is covered; MS (EI): m/z (%): 262 (100) [M+], 233 (5), 181 (25); elemental
analysis calcd (%) for C18H14O (262.3): C 82.42, H 5.38; found: C 82.56, H 5.29.
13-exo-(2-benzo[b]furyl)-11,12-dihydro-6,11-methano-6H-benzo[4,5]cyclohepta[1,2-
b]benzo[d]furan (exo-2b) [14]: Yield 20.0%; colourless crystals, m.p. 158-159 ºC; Rf = 0.31
(petroleum ether/CH2Cl2 7:3); UV (EtOH) λmax (ε) 304 (37153), 254 (2754), 217 nm (14791);
1H NMR (300 MHz, CDCl3) δ 7.61 (d, J = 7.2 Hz, 1H), 7.32-7.43 (m, 3H, H-2; H-2’), 7.00-
7.27 (m, 8H), 6.15 (s, 1H; H-6'), 4.49 (s, 1H; H-A), 4.04 (d, J = 4.8 Hz, 1H; H-B), 3.83 (s,
13
1H; H-E), 3.50 (dd, J = 4.8, 17.1 Hz, 1H; H-C), 2.94 (d, J = 17.1 Hz, 1H; H-D); C NMR
(CDCl3) δ 159. 5 (s), 154. 5 (s), 154.4 (s), 150.15 (s), 149.4 (s), 142.2 (s), 128.5 (s), 127.1 (d),
126.8 (d), 126.3 (s), 124.6 (d), 123.4 (d), 123.1 (d), 122.5 (d), 122.5 (d), 121.7 (s), 121.4 (d),
120.6 (d), 117.9 (d), 111.1 (d), 110.7 (d), 102.5 (d), 52.7 (d; C-B), 44.8 (d; C-C), 42.0 (d; C-
A), 31.8 (t; C-DE); MS (ESI): m/z (%): 362.5 (30) [M+], 145.2 (80), 83.3 (100); elemental
analysis calcd (%) for C26H18O2 (362.4): C 86.16, H 5.01; found: C 86.03, H 5.13.
6,25-dioxaheptacyclo[15.11.0.0²,¹⁴.0⁵,¹³.0⁷,¹².0¹⁸,²⁶.0¹⁹,²⁴]octacosa-1(17),2(14),3,5(13),7,9,
11,15,18(26),19(24),20,22,27-tridecaene (16): Yield 15 %; Rf =0.36 (petroleum ether /
dichloromethane = 4:1); colourless crystals; mp 145 - 148 ºC; UV (EtOH) λmax (ε) 374 (945),
355 (1714), 346 (4709), 330 (5307), 315 (3940), 300 (4161), 275 (6992), 253 (7860), 239
1
(10208); H NMR (600 MHz, CDCl3): δ 8.90 (d, J = 9.2 Hz, 1H, H-ar), 8.89 (s, 1H, H-ar),
8.52 (dd, J = 7.7; 1.3 Hz, 1H, H-ar), 7.97 (d, J = 9.2 Hz, 1H, H-ar), 7.74 (dd, J = 7.7; 1.3 Hz,
1H, H-ar), 7.56 (dd, J = 7.7; 1.3 Hz, 1H, H-ar), 7.53 (dd, J = 7.7; 1.3 Hz, 1H, H-ar). 13C NMR
(CDCl3, 150 MHz) δ 135.0 (s), 132.5 (s), 132,4 (s), 128.6 (s), 128.5 (s), 127.7 (d), 126.9 (s),
126.3 (s), 126.1 (d), 124.3 (d), 122.7 (d), 122.4 (d), 121.8 (d), 120.4 (q), 118.6 (d), 110.6 (d);
IR 2346, 2160, 1774, 1655 cm-1; HRMS: M+calcd 359.1072; M+found 359.1070.
15

ACCEPTED MANUSCRIPT
endo-12-(1-benzofuran-2-yl)-9-phenyltricyclo[6.3.1.0²,⁷]dodeca-2(7),3,5-trien-10-one
(endo-17): Yield 2 %; Rf = 0.28 (petroleum ether / dichloromethane = 4:1); colourless
crystals; mp 190 - 193 ºC; UV (EtOH) λmax (ε) 284 (1757), 277 (1891), 252 (5648); 1H NMR
(600 MHz, CDCl3) δ 7.43 (d, J = 7.4 Hz, 1H, H-ar), 7.35 (dd, J = 7.4; 0.8 Hz, 1H, H-ar), 7.10-
7.28 (m, 7H, H-ar), 7.05 (d, J = 7.4 Hz, 1H, H-ar), 6.90 (d, J = 7.4 Hz, 1H, H-ar), 6.79 (d, J =
7.4 Hz, 1H, H-ar), 6.66 (dt, J = 7.4; 0.8 Hz, 1H, H-ar), 6.34 (s, 1H, H-f), 4.67 (d, J = 8.8 Hz,
H-E/F), 4.53 (dd, J = 11.8; 5.7 Hz, H-B), 4.16 (d, J = 8.8 Hz, H-E/F), 3.72 (t, J = 8.8 Hz, H-
13
A), 3.40-3.50 (m, 2H, H-C, H-D). C NMR (CDCl3, 150 MHz) δ 180.0 (s), 159.8 (s), 155.6
(s), 154.4 (s), 136.0 (s), 133.9 (s), 128.4 (2d), 128.2 (d), 127.8 (s), 127.3 (d), 127.0 (2d), 126.8
(d), 126.2 (d), 123.2 (d), 122.0 (d), 120.6 (d), 120.1 (d), 110.3 (d), 109.8 (d), 57.7 (d), 50.0
(d), 46.2 (d), 42.7 (d), 37.3 (t); IR 1977, 1655, 1459, 745 cm-1.
exo-12-(1-benzofuran-2-yl)-9-phenyltricyclo[6.3.1.0²,⁷]dodeca-2(7),3,5-trien-10-one (exo-
18): Yield 20 %; Rf =0.11 (petroleum ether / dichloromethane = 4:1); colourless crystals; mp
1
196 - 198 ºC; UV (EtOH) λmax (ε) 284 (2723), 277 (2722), 250 (5809); H NMR (600 MHz,
CDCl3) δ 7.46 (d, J = 7.4 Hz, 1H, H-ar), 7.39 (dd, J = 7.4; 0.8 Hz, 1H, H-ar), 7.10-7.28 (m,
7H, H-ar), 7.03 (d, J = 7.4 Hz, 1H, H-ar), 6.90 (d, J = 7.4 Hz, 1H, H-ar), 6.74 (d, J = 7.4 Hz,
1H, H-ar), 6.68 (dt, J = 7.4; 0.8 Hz, 1H, H-ar), 6.42 (s, 1H, H-f), 4.61 (dd, J = 10.0; 3.5 Hz,
1H, H-B), 4.34 (d, J = 8.3 Hz, 1H, H-E/F), 4.27 (d, J = 9.3 Hz, 1H, H-E/F), 3.77 (dd, J = 9.3;
8.3 Hz, 1H, H-A), 3.48 (dd, J = 15.4; 10.0 Hz, 1H, H-C/D), 3.32 (d, J = 15.4 Hz, 1H, H-C/D).
13C NMR (CDCl3, 150 MHz) δ 180.0 (s), 159.6 (s), 155.9 (s), 154.5 (s), 135.5 (s), 128.6 (d),
127.8 (s), 127.2 (d), 126.6 (d), 126.3 (2d), 126.1 (d), 125.9 (s), 123.3 (d), 122.1 (d), 120.7
(2d), 120.2 (d), 110.4 (d), 110.3 (d), 103.5 (d), 57.1 (d), 48.1 (d), 48.8 (d), 42.0 (d), 35.8 (t);
IR 2160, 1735, 1671 cm-1; HRMS: M+calcd 365.1542; M+found 365.1536.
8,10-dimethylpyreno[4,5-b]furan (20): due to instability of the compound, it was not
possible to analyze it completely; Yield 11 %; Rf = 0.55 (petroleum ether / dichloromethane =
9:1); colourless oil; 1H NMR (CDCl3; 600 MHz) δ 8.31 (dd, JF,G= 7.8 Hz, 1H, H-G), 8.09 (dd,
JE,F = 7.5 Hz, 1H, H-E), 8.02 (d, JA,B = 7.7 Hz, 1H, H-B), 8.0 (dd, J = 14.8; 8.7 Hz , 2H, H-C,
H-D), 7.99 (t, JF,G = 7.8 Hz; JF,E = 7.5 Hz, 1H, H-F), 7.85 (dd, JA,B = 7.7; J = 1.0 Hz, 1H, H-
13
A), 7.07 (s, 1H, H-f), 3.28 (s, 3H, -CH3), 2.69 (s, 3H, -CH3); C NMR (CDCl3, 150 MHz) δ
131.8 (s), 129.6 (s), 129.5 (s), 128.6 (d), 127.2 (d), 126.4 (s), 126.2 (d), 125.2 (d), 123.6 (d),
123.2 (d), 122.4 (s), 122.3 (s), 120.1 (s), 119.6 (d), 117.2 (s), 113.5 (s), 101.8 (d), 13.6 (q); IR
2160, 1718, 1685, 1458 cm-1.
16

ACCEPTED MANUSCRIPT
2-methyl-5-[3-(5-methylfuran-2-yl)-3,4-dihydronaphthalen-2-yl]furan (21): Yield 17 %;
Rf = 0.39 (petroleum ether / dichloromethane = 9:1); colourless oil; UV (EtOH) λmax (ε) 349
1
(10668), 334 (13416), 319 (10668, sh), 295 (7058, sh), 252 (5450, sh), 228 (10946); H NMR
(CDCl3; 600 MHz) δ 7.53 (d, J = 7.34 Hz, 1H), 7.16-7.25 (m, 3H, H-ar), 6.85 (d, J = 1.6 Hz,
1H), 6.11 (d, J = 3.0 Hz, 1H), 5.90 (d, J = 2.7 Hz, 1H), 5.72 (s, 2H), 4.63 (d, JB,X = 8.4, 1H,
H-X), 3.44 (dd, JA,X = 8.4; JA,B = 16.7 Hz, 1H, H-A), 3.16 (d, JA,B = 16.8 Hz, 1H, H-B), 2.27
13
(s, 3H, -CH3), 2.24 (s, 3H, -CH3); C NMR (CDCl3, 150 MHz) δ 155.3 (s), 151.7 (s), 151.4
(s), 146.0 (s), 143.9 (s),143.9 (s), 141.6 (s), 140.4 (s), 126.2 (d), 125.8 (d), 124.0 (d), 120.6
(d), 106.3 (d), 105.3 (d), 105.1 (d), 104.4 (d), 103.8 (d), 52.3 (d), 41.4 (d), 38.0 (s); IR 2160,
1794, 1522, 1459 cm-1; HRMS: M+calcd 291.1385; M+found 191.1372.
3-[3-(furan-3-yl)-3,4-dihydronaphthalen-2-yl]furan (22): Yield 15 %; Rf = 0.60 (petroleum
ether / dichloromethane = 9:1); colourless oil; UV (EtOH) λmax (ε) 311 (1642), 238 (2562,
1
sh); H NMR (CDCl3; 600 MHz) δ 7.52 (s, H-f), 7.42 (t, J = 1.8 Hz, 1H, H-f), 7.07-7.16 (m,
6H, 5H-ar, H-f), 6.80 (s, H-f), 6.68 (d, J = 1.8 Hz, 1H, H-f), 6.11 (d, J = 1.8 Hz, 1H, H-f),
3.81 (d, J = 6.7 Hz, 1H, H-X), 3.38 (dd, J = 15.6; 6.7 Hz, 1H, H-A), 2.96 (dd, J = 15.6; 1.5
Hz, 1H, H-B), 13C NMR (CDCl3, 150 MHz) δ 136.6 (s), 133.5 (s), 132.4 (s), 132.3 (s), 131.9
(s), 128.5 (d), 128.1 (d), 127.5 (d), 127.0 (d), 126.7 (d), 126.2 (d), 125.6 (d), 125.3 (d), 121.8
(d), 109.6 (d), 107.2 (d), 38.4 (d), 37.2 (d), 35.0 (t), 32.6 (d), 29.2(d); IR 2160, 1655, 1542
cm-1; HRMS: M+calcd 263.1072; M+found 263.1072.
17

ACCEPTED MANUSCRIPT
Literature:
[1] Sirerol J. A., Rodríguez M. L., Mena S., Asensi M. A., Estrela J. M., Ortega A. L.
OXID MED CELL LONGEV 2016; 1.
[2] Reinisalo M., Kårlund A., Koskela A., Kaarniranta K., Reijo Karjalainen O. OXID
MED CELL LONGEV 2015; 1.
[3] Jørgensen K. B. Molecules 2010;15:4334.
[4] Vidaković D., Škorić I., Horvat M., Marinić Ž., Šindler-Kulyk M. Tetrahedron 2008;
64:3928.
[5] Šindler-Kulyk M., Špoljarić L., Marinić Ž. Heterocycles 1989; 29:679.
[6] Šindler-Kulyk M., Kragol G., Piantanida I., Tomšić S., Vujković Cvijin I., Marinić,
Ž., Metelko B. Croat. Chem. Acta 1996; 69:1593.
[7] Šindler-Kulyk M., Škorić I., Tomšić S., Marinić Ž., Mrvoš-Sermek D. Heterocycles
1999; 51:1355.
[8] Škorić I., Marinić Ž., Šindler-Kulyk M. Heterocycles 2000; 53:55.
[9] Šindler-Kulyk M., Tomšić S., Marinić Ž., Metelko B. Recl. Trav. Chim. Pays-Bas
1995; 114:476.
[10]
[11]
Basarić N., Marinić Ž., Šindler-Kulyk M. J. Org. Chem. 2003; 68:7524.
Basarić N., Iveković D., Zimmermann B., Marinić Ž., Klowski K.,
Rademacher P., Šindler-Kulyk, M. Journal Photochem. Photobiol. A: Chemistry
2003; 154:123.
[12]
Vuk D., Marinić Ž., Molčanov K., Kojić-Prodić B., Šindler-Kulyk M.
Tetrahedron 2012; 68:6873.
[13]
Vuk D., Marinić Ž., Molčanov K., Kojić-Prodić B., Šindler-Kulyk M. Croat.
Škorić I., Basarić N., Marinić Ž., Višnjevac A., Kojić-Prodić B., Šindler-Kulyk
Chem. Acta 2012; 85:425.
[14]
M. Chem. Eur. J. 2005; 11:534.
18

ACCEPTED MANUSCRIPT
[15]
Basarić N., Tomšić S., Marinić Ž., Šindler-Kulyk M. Tetrahedron 2000;
56:1587.
[16]
Basarić N., Marinić, Ž., Šindler-Kulyk M. Tetrahedron Lett. 2001; 42:3641.
Basarić N., Višnjevac A., Kojić-Prodić B., Griesbeck A., Šindler-Kulyk M.
[17]
Photochem. Photobiol. Sci. 2002; 1:1017.
[18]
Bonačić-Koutecký V., Bruckmann P., Hiberty P., Koutecký J., Leforestier C.,
Salem L. Angew. Chem. 1975; 87:599.
[19]
Presser M., Coquerel Y., Rodriguez J. Chem. Rev. 2013; 113:525.
Rokade Y. B., Sayyed R.Z. Rasāyan J. Chem. 2009, 2:972.
Craig R. A. II, Stoltz B. M. Chem. Rev. 2017, 117:7878.
Miyashita M. Pure Appl. Chem. 2007, 79, 4:651.
[20]
[21]
[22]
19

ACCEPTED MANUSCRIPT
Acknowledgment
University of Zagreb short term scientific support under the title “Synthesis and
functionalization of novel (hetero)polycyclic photoproducts” are gratefully acknowledged.
20

ACCEPTED MANUSCRIPT
Synthesis of new furan polycycles via photochemical reaction in neutral and acidic medium
Highlights
•
Photoreactivity of the starting material changes upon different pH value
•
•
The change of the heteroatom affects the course of the photochemical reaction
Novel polycyclic photoproducts were synthesized and characterized