Photooxygenation of furans in water and ionic liquid solutions

Article abstract of DOI:10.1039/b914726h

Photooxygenation of differently functionalized furans is investigated in aqueous solutions and in ionic liquids [emim]Br and [bmim]BF₄. The reaction is generally selective and the final products derive from rearrangement of the intermediate endoperoxides, depending mainly on the polarity and/or nucleophilic nature of the solvent.

Full text of DOI:10.1039/b914726h

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/greenchem | Green Chemistry
Photooxygenation of furans in water and ionic liquid solutions†
Anna Astarita, Flavio Cermola, Marina DellaGreca, Maria Rosaria Iesce,* Lucio Previtera and
Maria Rubino*
Received 21st July 2009, Accepted 24th September 2009
First published as an Advance Article on the web 27th October 2009
DOI: 10.1039/b914726h
Photooxygenation of differently functionalized furans is investigated in aqueous solutions and in
ionic liquids [emim]Br and [bmim]BF4. The reaction is generally selective and the final products
derive from rearrangement of the intermediate endoperoxides, depending mainly on the polarity
and/or nucleophilic nature of the solvent.
Introduction
Results and discussion
Much of the attention of the scientific community is currently
directed toward developing new benign and clean processes
or products.1 In this context, dye-sensitized photooxygenation
appears one of the most promising oxidation routes: i) the
sole oxygen source is natural triplet oxygen, ii) a complete
atom economy can be reached since both oxygen atoms are
incorporated in the final products, iii) reactions of the reactive
species, singlet oxygen, are highly selective and show all the
kinetic properties of pericyclic reactions.2,3 One drawback is
that singlet oxygen has its longest lifetimes in environmentally
problematic solvents such as halogenated hydrocarbons or
benzene.4
Among the photooxygenation applications, the reactions of
furans have a prominent role due to the wide number of
related synthetic routes.2,5,6 There are, for example, many reports
where butenolides or ene-diones obtained by dye-sensitized
photooxygenation of furans have been incorporated into the
framework of more complex molecules.2,5,6
Here, we report an investigation on the dye-sensitized pho-
tooxygenation of furans in green solvent water and in room-
temperature ionic liquids (ILs). Currently, great attention is
devoted to the use of ionic liquids as solvents due to their
characteristics such as low viscosity, low vapour pressure and
ability to dissolve organic compounds, salts and metals.7 Very
few studies concerning the use of ionic liquids in dye-sensitized
photooxygention have been performed so far.8,9 Recent studies
have shown that singlet oxygen quenching rate constants are
similar in the organic solvent CH3CN and in ionic liquids
containing 1,3-dialkylimidazolium ions.9 To our knowledge, our
investigation is the first one on the dye-sensitized photooxygena-
tion of furans in ionic liquids.
Irradiations were performed by a classical photooxygena-
tion procedure2 in water, 1-ethyl-3-methylimidazolium bromide
([emim]Br) and 1-butyl-3-methylimidazolium tetrafluoroborate
([bmim]BF4). Because [emim]Br is solid at rt, 10% (p/v)
acetonitrile was added to obtain a liquid mixture. This solvent
was also used as co-solvent with water (1 : 1 v/v) to solubilize
all furans. Photooxygenation in pure acetonitrile was performed
for comparison. We chose differently functionalized furans since
close structure–reactivity relationships have been observed in
the rearrangements of the related endoperoxides and the type of
final product depends mainly on the nature of a,a¢-substituents,
from hydrogen to alkyl groups, from aryl to alkoxy groups,
and/or solvent.2,5 Furans used, reaction conditions and product
distributions are reported in Table 1. The photooxygenations
were generally complete within 2 h. Identification of products
was made by comparison of NMR data with those reported in
the literature (Table 1). The new compounds 6d and 6e were
characterized by physical means. NMR data for compound 3b10
were also described because they are reported in a non-accessible
journal.
No appreciable differences in the reaction times were observed
when using these green solvents, except for [bmim]BF4, when
compared to those in halogenated solvents (generally 1–2 h), and
this highlights the extraordinary reactivity of the furan system
towards singlet oxygen, even in the protic water. The longer times
required for furans 1a, 1b and 1g were expected due to the low
nucleophilicity of these furans.11
In contrast to water and solid IL [emim]Br, which generally
give good selectivity and yields, in the liquid IL [bmim]BF4, the
reaction of unsubstituted furans does not occur and the reac-
tion of methylsubstituted furans leads to polymeric materials
(Table 1). Nevertheless, [emim]BF4 is a good solvent in the series
of arylsubstituted furans 1g–j. Enediones 7, lactones 2 and 3,
and epoxides 9 are the main products. Only endo-peroxide 8g
has been detected, according to the well-known thermal stability,
even at room temperature, of fully substituted endoperoxides,12
but the structures of all products indicate that endo-peroxides
8 are the key intermediates in the reactions of all furans 1
(Scheme 1).2,5
Dipartimento di Chimica Organica e Biochimica, Complesso
Universitario Monte Sant’Angelo, Via Cinthia 4, I-80126, Naples, Italy.
E-mail: iesce@unina.it; Fax: +3908 674393; Tel: +39 08 674334,
E-mail: marubino@unina.it; Fax: +39081674393; Tel: +39081674333
† This work has been presented at the 2nd International IUPAC
Conference on Green Chemistry (IUPAC ICGC-2), held in Moscow-
St. Petersburg, Russia, 14–19 September, 2008.
2030 | Green Chem., 2009, 11, 2030–2033
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
Table 1 Photooxygenation of furans 1 (0.007 M) at 0–10 ◦C under different conditions
Product (%)a
Water/CH3CN
(1 : 1)c
[emim]Br/
CH3CNb,d
b
Entry R1
R2
H
R3
R4
CH3CNb
[bmim]BF4
Ref.
18
a
b
H
H
COPh
COPh
2a (40%)e
2a (> 90%)
No reaction
No reaction
No reaction
CO2Me
CH2OH
Me
H
H
H
H
H
H
2b (80%)
3b (16%)
2b (50%)
3b (45%)
—
10
22
3b (55%)f
c
H
H
4c (>90%)
—
4c (78%)
5c (15%)
4c (90%)
5c (trace)
4c (>90%)
—
11
23
d
Polymeric
material
6d (> 90%)
—
Polymeric
material
24
25
19
.
2d (> 90%)
e
f
Me
Me
Me
Me
H
H
H
Polymeric
material
6e (55%)
7e (40%)
—
Polymeric
material
7e (> 80%)
Polymeric
material
7f (> 90%)
7f (> 90%)
Polymeric
material
g
h
i
Ph
Ph
CO2Me
CO2Et
CO2Me
H
CO2Me
H
8g (> 90%)
8g (> 90)
cis-7g (78%)
8g (38%)g
12
26
trans-7g (16%)
Ph
Ph
7h (22%)
9h (73%)
7h (25%)
9h (70%)
7h (67%)
9h (25%)
7h (68%)
9h (28%)
12
4-Me-C6H4
4-Me-C6H4
OMe
OMe
H
7i (60%)
9i (38%)
7i (65%)
9i (10%)
7i (45%)
9i (35%)
7i (> 90%)
—
17
27
j
CO2Me
7j (45%)
9j (43%)
7j (> 90%)
—
7j (> 90%)
—
7j (56%)
9j (38%)
21
a Yield of pure product isolated by preparative TLC. b Rose bengal (10-4 M) as sensitizer. c Methylene blue (10-4 M) as sensitizer. d [Emim]Br (0.5 M).
e 1a (50%). f 1b (40%). g 1g (55%).
Hence, the nature of solvents does not influence the addition
mode of singlet oxygen to the heterocycle, which undergoes
[4+2] cycloaddition, but has a predominant role in the fate
of the cycloadduct endoperoxide 8. Indeed, due to the high
polarity and/or nucleophilic nature of the solvent, the endo-
peroxide decomposition leads mainly to products formed by
ionic mechanisms such as enediones 75,13 and, from furans with
at least one hydrogen at a-position, to 2(5H)-furanones 2 or 3
which are favoured by nucleophilic solvents (Kornblum deLa
Mare rearrangement) (Scheme 1).2,5,11 In the photooxygenations
This journal is
The Royal Society of Chemistry 2009
Green Chem., 2009, 11, 2030–2033 | 2031
©

View Article Online
Table 2 Product distributions in the photooxygenation of furfuryl alcohol 1c in aqueous solutionsa
Product (%)b
Entry
Solvent
1
2
3
4
5
6
CH3CN
Water–CH3CN
Water
Water/pH 2
Water/pH 4
Water/pH 9
—
—
—
100
33
—
100
84
65
—
50
—
—
16
35
—
17
100
a 0.007 M, rose bengal (entry 1) and methylene blue (entries 2–6) as sensitizers, 2 h. b Percentage yield deduced by 1H NMR.
Scheme 2 Secondary routes.
In conclusion, the photooxygenation of furans in aqueous
solution and in ionic liquids appears promising due to the mild
conditions and high selectivity and for leading to interesting
compounds. Enediones 7 are useful building blocks in organic
synthesis14 and the hydroxyfuranone system is present in a wide
range of natural and synthetic products, often with biological
properties.6,15 Even compound 5c is a useful synthon.6 For
these products, photooxygenation is a good alternative to
other methods which employ oxidizing reagents including N-
bromosuccinimide, m-chloroperbenzoic acid, sodium chlorite or
TBHP.6 The use of green solvents improves the photochemical
method, even reducing the reaction steps. Indeed, for example,
enediones 7 are generally obtained in two steps by low temper-
ature photooxygenation followed by sulfide reduction.16,17
Scheme 1 The primary phototransformation pathways.
of arylsubstitued furans 1h–j, epoxides 9h–j are also found.
Ionic mechanisms and/or, for a,a¢-diarylfurans,13 a concerted
mechamism has been suggested for the formation of these
compounds.5,13 The prevalence of the concerted mechanism
in CH3CN and in water–CH3CN for diarylfuran 1h should
account for the different product selectivity in favour of epoxide
9h observed in the molecular solvents with respect to ionic
liquids. Compounds 6d,e present only in water, derive from the
corresponding 7d,e by hydration which is accelerated by light,
as proven by control experiments starting from 7e.‡ Moreover,
butenolide 4c is the decomposition product from the labile
undetected 3c, while pyranone 5c is the cyclization product from
7c (Scheme 2).
Stimulated by good results in water–CH3CN, we oxygenated
the water-soluble furan 1c exclusively in water and at different
pHs. In Table 2, we report these results and, for comparison,
those in CH3CN and in water–CH3CN. Increasing water content
and basicity increase the yield of pyranone 5c. The reaction does
not occur at pH 2, probably due to the protonation of furan
and, hence, to the decreased nucleophilicity of the system in the
reaction with the electrophilic singlet oxygen.
Experimental
Materials
Furans 1b–e (Aldrich), ionic liquids (Fluka) and sensitizers
(Fluka) were commercial materials. Furans 1a,18 1f,19 1g,12 1h,20
1i,17 and 1j21 were prepared according to the known procedures.
Typical photooxygenation procedure. 0.007 M concentra-
tions were prepared starting from 0.35 mmol of each furan
using CH3CN, H2O–CH3CN (1 : 1 v/v) and the solid ionic liquid
[emim]Br/CH3CN (10% p/v) as solvents while 0.07 mmol except
for furans 1b–1e (0.14 mmol) were used when employing liquid
ionic liquid [bmim]BF4. In the latter case, the solution was
prepared by dissolving furan 1 in a few microliters of CH3CN,
adding ionic liquid [bmim]BF4, and then evaporating CH3CN in
‡ Hydration of (Z)-hex-3-ene-2,5-dione (7e): compound 7e (15 mg) was
dissolved in 13 ml of H2O–CH3CN (1 : 1, 10-2 M). An aliquot was
irradiated for 2 h and treated as reported in the photooxygenation
procedure. 1H NMR analysis of the residue showed the presence of
compound 7e and 6e in ca. 1 : 3 molar ratio. The other aliquot was kept
in the dark for 4 h. Solvent evaporation gave a residue consisting of 7e
and 6e in ca. 1 : 1 molar ratio (by 1H NMR).
2032 | Green Chem., 2009, 11, 2030–2033
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
vacuum. Each solution of 1 was irradiated with a halogen lamp
(General Electric, 650 W) in the presence of methylene blue or
rose bengal (1 ¥ 10-4 M) while dry oxygen was bubbled through
the solution. Methylene blue was used as the photosensitizer for
irradiation experiments in H2O–CH3CN (1 : 1), while rose bengal
was used as photosensitizer for irradiations in CH3CN and ionic
liquids. The temperature was maintained at 0–5 ◦C by immersion
of the reactor (a Pyrex round-bottom flask) in an acetone bath
thermostated by a Cryocool. The progress of each reaction was
checked by periodically monitoring (TLC or 1H NMR) the
disappearance of 1 (generally 2 h). The incomplete reactions
were stopped after 2 h of irradiation. Reaction mixtures obtained
from irradiation in CH3CN and H2O–CH3CN were evaporated
in vacuum. Mixtures from irradiation in CH3CN with the
solid ionic liquid [emim]Br were evaporated to remove CH3CN
and the residues were extracted with diethyl ether (six times).
Mixtures from [bmim]BF4 were extracted with diethyl ether
(six times). Each residue was analyzed by 1H NMR. Yields
were deduced by 1H NMR and confirmed by preparative TLC
chromatography. Known reaction products were identified by
comparison of spectral data with those reported (see ref. in
Table 1). Spectral data for 3b, not available,10 and for new 6d and
6e are reported below. Compound 6d was obtained with a purity
of 85% since it undergoes slow spontaneous polymerization,
hence only its NMR spectra are described; its structure was
assigned by comparison of these spectral data with those of
compound 6e.
1H NMR. Experiments using the same concentrations of furan
1c were carried out at pH 2, 4 and 9 by adjusting the pH with
HCl 0.2 M and KOH 0.2 M. Each solution was treated as above
and analyzed by 1H NMR.
Notes and references
1 J. Clark, D. MacQuarrie, Handbook of Green Chemistry & Technol-
ogy, Blackwell Science, 2002.
2 M. R. Iesce, Synthetic Organic Photochemistry, A. G. Griesbeck,
J. Mattay, Eds., Vol. 12, Marcel Dekker, New York, 2005, p. 292.
3 E. Clennan, Synthetic Organic Photochemistry, A. G. Griesbeck,
J. Mattay, Eds., Vol. 12, Marcel Dekker, New York, 2005, p. 365.
4 B. M. Monroe, Singlet O2, A. A. Frimer, Ed., Vol. 1, CRC Press,
Boca Raton (FL), 1985, p. 177.
5 M. R. Iesce, F. Cermola and F. Temussi, Curr. Org. Chem., 2005, 9,
109–139.
6 T. Montagnon, M. Tofi and G. Vassilikogiannakis, Acc. Chem. Res.,
2008, 41, 1001; P. Merino, T. Tejero, J. I. Delso and R. Matute, Curr.
Org. Chem., 2007, 11, 1076–1091.
7 P. Wasserscheid, T. Welton, Ionic Liquids in Synthesis, P. Wasser-
scheid, T. Welton, Eds., WILEY-VCH, Germania, 2003.
8 K. Swiderski, A. McLean, C. M. Gordon and D. Huw Vaughan,
Chem. Commun., 2004, 2178–2179; N. Gandra, A. T. Frank, O. Le
Gendre, N. Sawwan, D. Aebisher, J. F. Liebman, K. N. Houk, A.
Greer and R. Gao, Tetrahedron, 2006, 62, 10771–10776.
9 E. Baciocchi, C. Chiappe, T. Del Giacco, C. Fasciani, O. Lanzalunga,
A. Lapi and B. Melai, Org. Lett., 2009, 11, 1413–1416.
10 Y. H. Kuo, Chem. Express, 1986, 1, 475–478.
11 K. Gollnick and A. Griesbeck, Tetrahedron, 1984, 41, 2057–
2068.
12 M. L. Graziano, M. R. Iesce and R. Scarpati, J. Chem. Soc., Perkin
3b:10 oil (found: C, 45.6, H, 3.8. C6H6O5 requires C, 45.58;
H, 3.82%); nmax(film)/cm-1 1792, 1759 and 1257; dH (500 MHz;
CDCl3) 3.89 (3 H, s, OCH3), 6.34 (1 H, d, J 5.6, H-3), 6.87 (1
H, s, H-5), 7.32 (1 H, d, J 5.6, H-4); dC (125 MHz; CDCl3) 55.6
(q, OCH3), 96.3 (d, C-5), 125.4 (d, C-3), 148.6 (d, C-4), 153.5 (s,
CO), 169.0 (s, CO2); m/z (EI) 157 [M - 1]+, 99 [M - CO2CH3]+,
83 [M - OCO2CH3]+.
6d (purity of 85%): dH (500 MHz; CDCl3) 1.42 (3 H, s, CH3),
5.40 (1 H, d, J 3.6 Hz, H-3), 6.00 (1 H, dd, J 10.2 and 3.6 Hz,
H-4), 6.08 (1 H, d, J 10.2 Hz, H-5); dC (125 MHz; CDCl3) 22.9
(CH3), 90.6 (C-2), 95.4 (C-5), 124.5 (C-3), 131.3 (C-4).
Trans. 1, 1982, 2007–2012.
13 M. L. Graziano, M. R. Iesce, S. Chiosi and R. Scarpati, J. Chem.
Soc., Perkin Trans. 1, 1983, 2071–2074.
14 G. Piancatelli, M. D’Auria and F. D’Onofrio, Synthesis, 1994, 867–
889.
15 P. Esser, B. Pohlmann and H.-D. Scharf, Angew. Chem., Int. Ed.
Engl., 1994, 33, 2009–2023.
16 M. L. Graziano, M. R. Iesce, B. Carli and R. Scarpati, Synthesis,
1983, 125–126.
17 M. R. Iesce, F. Cermola, A. Piazza, R. Scarpati and M. L. Graziano,
Synthesis, 1995, 439–443.
18 M. L. Graziano and M. R. Iesce, Synthesis, 1985, 1151–1153.
19 F. Cermola, M. R. Iesce and G. Buonerba, J. Org. Chem., 2005, 70,
6503–6505.
20 A. P. Dunlop, F. N. Peters, The Furans, Reinhold Publishing, New
6e white solid (found: C, 55.4; H, 7.6. C6H10O3 requires
York, 1953, p. 579.
C, 55,37; H, 7.75%); mp 100.9–103.5 ◦C (from CH3OH);
21 M. R. Iesce, F. Cermola, F. Giordano, R. Scarpati and M. L.
Graziano, J. Chem. Soc., Perkin Trans. 1, 1994, 3295–3298.
22 A. Astarita, F. Cermola, M. R. Iesce and L. Previtera, Tetrahedron,
2008, 64, 6744–6748.
23 O. Achmatowicz JR, P. Bukowski, B. Szechner, Z. Zwierzchowska
and A. Zamojski, Tetrahedron, 1971, 27, 1973–1996.
24 L. Cottier, G. Descotes, H. Nigay, J.-C. Parron and V. Gre´goire, Bull.
Soc. Chim. Fr., 1986, 5, 844–850.
25 T. Noguchi, K. Takayama and M. Nakano, Biochem. Biophys. Res.
Commun., 1977, 78, 418–423.
26 P. Yu. Savechenkov, A. V. Vasil’ev and A. P. Rudenko, Russ. J. Org.
Chem., 2004, 40, 1279–1283.
n
max(film)/cm-1 3407, 3347, 1364 and 1110; dH (500 MHz;
CD3OD) 1.37 (6 H, s, 2 ¥ CH3), 4.87 (br s, OH), 5.89 (2 H, s, H-3
and H-4); dC (125 MHz; CD3OD) 24.2 (2 ¥ CH3), 96.3 (C-2 and
C-5), 130.6 (C-3 and C-4); m/z (EI) 130 [M]+, 112 [M - H2O]+.
Photooxygenation of 1c in water at different pH. Furan 1c
(50 mg) was dissolved in water (65 ml) and irradiated in the
presence of methylene blue (1 ¥ 10-4 M) as above. After 2 h, the
reaction mixture was extracted with ethyl acetate (3 ¥ 40 ml) and
the organic layer anidrified with dry Na2SO4. It was evaporated
under vacuum obtaining 45 mg of a residue that was analyzed by
27 M. R. Iesce, F. Cermola, A. Guitto, R. Scarpati and M. L. Graziano,
Synlett, 1995, 1161–1162.
This journal is
The Royal Society of Chemistry 2009
Green Chem., 2009, 11, 2030–2033 | 2033
©