Green synthetic approaches to furoylnaphthohydroquinone and juglone

Article abstract of DOI:10.4067/S0717-97072014000200012

The synthesis of two valuable precursors of biological active compounds named 2-(furan-2-yl)-1,4-dihydroxynapthohydroquinone 2 and 5-hydroxy-1,4-naphthoquinone (4, juglone) via solar photo-induced reactions from 1,4-naphthoquinone 1 and 1,5-dihydroxynaphthalene 3 in green solvent media is reported. When t-butyl alcohol and the binary t-ButOH/DMK and ternary i-PrOAc/DMK/MEK solvent mixtures were used, acylhydroquinone 2 was isolated in yields of 80, 83 and 77%, respectively. The sensitized photooxygenation of 3 "on water" and in water containing sodium dodecyl sulfate produce juglone 4 in 81 and 39% yields respectively.

Full text of DOI:10.4067/S0717-97072014000200012

J. Chil. Chem. Soc., 59, Nº 2 (2014)
GREEN SYNTHETIC APPROACHES TO FUROYLNAPHTHOHYDROQUINONE AND JUGLONE
JULIO BENITES1,3*, MICHAEL CORTES1, LUIS MIRANDA1, CYNTHIA ESTELA1, DAVID RIOS1,
JORGE ARENAS2 and JAIME A. VALDERRAMA1,3*
1Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique, Chile.
2Facultad de Recursos Naturales Renovables, Universidad Arturo Prat. Casilla 121. Iquique, Chile.
3Instituto de Ciencias Exactas y Naturales (ICEN), Universidad Arturo Prat, Casilla 121, Iquique, Chile.
ABSTRACT
The synthesis of two valuable precursors of biological active compounds named 2-(furan-2-yl)-1,4-dihydroxynapthohydroquinone 2 and 5-hydroxy-1,4-
naphthoquinone (4, juglone) via solar photo-induced reactions from 1,4-naphthoquinone 1 and 1,5-dihydroxynaphthalene 3 in green solvent media is reported.
When t-butyl alcohol and the binary t-ButOH/DMK and ternary i-PrOAc/DMK/MEK solvent mixtures were used, acylhydroquinone 2 was isolated in yields of
80, 83 and 77%, respectively. The sensitized photooxygenation of 3 “on water” and in water containing sodium dodecyl sulfate produce juglone 4 in 81 and 39%
yields respectively.
Keywords: Solar light; Photoacylation; Photooxygenation; Green chemistry
General procedure: Asolution of 1,4-naphthoquinone 1 (1 mmol), furfural
(7.5 mmol) and the required “preferred Pfizer solvent” (10 mL) into a Pyrex
tube was gently bubbled with nitrogen for 2 min. The tube was sealed with a
septum and then irradiated with sunlight for five days (total illumination time:
30 h; 800–1150 Watts/m2; November–March). The solvent(s) was removed
under reduced pressure and the residue was chromatographed on silica gel (3:1
petroleum ether/ethyl acetate).
INTRODUCTION
Photochemical reactions carried out with sunlight are particularly
interesting in the context of green chemistry due to substrate activation often
occurs without additional reagents, which diminishes formation of by products,
and the renewable nature of the energy source.1-4 Over the last few decades,
the growing demand for environmentally friendly technologies has attracted
rising attention in synthetic organic photochemistry.5,6 Solar photoacylation of
1,4-naphthoquinone 1 with furfural to give acylhydroquinone 2 and sensitized
photooxygenation of 1,5-dihydroxynaphthalene (1,5-DHN) 3 that provides
5-hydroxy-1,4-naphthoquinone (4, juglone) are two representative examples
of solar light-mediated synthesis in the field of quinoid compounds (Figure
1). Our continuous interest on quinone chemistry together the usefulness of
acylhydroquinone 2 and juglone 4 as precursors of biological active compounds
led us to study greener access to these compounds.
(1,4-Dihydroxynaphthalen-2-yl)(furan-2-yl)methanone 2: orange solid
1
mp, 188.5-189°C H RMN (400 MHz, DMSO-d6 + CDCl3): δ 13.61 (s, 1H,
1-OH), 9.13 (s, 1H, 4-OH), 8.34 (d, 1H, J = 7.8 Hz, 8- or 5-H), 8.12 (d, 1H, J=
7.8 Hz, 5- or 8-H), 7.50 (m, 5H, 6-, 7-H and furyl), 6.60 (s, 1H, 3-H). 13C NMR
(100 MHz, DMSO-d6 + CDCl3): δ 189.7, 156.3, 144.4, 142.2, 133.5, 132.7,
129.3, 128.8, 127.3, 125.6, 125.3, 123.6, 121.8, 111.3, 105.6. HRMS (APCI):
[M+H]+ calcd for C15H10O4: 254.05791; found: 254.05889.
Photooxygenation of 1,5-dihydroxynaphthalene 3 in different solvent
media.
General procedure: A solution of 1,5-dihydroxynaphthalene (3; 200 mg,
1.25 mmol), rose bengal (20 mg) and the required solvent (150 mL) into a round
bottom flask was irradiated by Light Emitting Diode lamps (LED: InGaN,
0.768 W, 42.24 lm, 530 nm) for 5 h at the same time a gently stream of air is
bubbled through the solution. Evaporated solvent(s) was frequently refilled.
Work up followed by column chromatography over silica gel (3:1 petroleum
ether/ethyl acetate) yield pure juglone 4 (orange solid, mp, 153-154°C; lit.7:
151-154°C). To evaluate the conversion of 3 and the yield formation of the
product 4, precursor 3 was recovered by column chromatography in each assay.
The identity of juglone 4 was corroborated by comparison of their TLC and
NMR´s spectral properties with those of an authentic sample.
Figure 1. Structure of precursors 1-3 and photoproducts 2-4.
Herein we wish to report results on the synthesis of acylhydroquinone 2 by
photoacylation of 1,4-naphthoquinone 1 with furfural by using solar irradiation
in different green solvent media. Greener synthetic approaches to prepare
juglone 4 by sensitized photooxygenation of 1,5-dihydroxynaphthalene 3 in
water media are also described.
RESULTS AND DISCUSSION
The solar-chemical experiments reported in this section were developed
in the Estación Experimental of Canchones, Universidad Arturo Prat, located
at latitude 20°26´43,80” S, 990 m above sea level in Chile’s northern desert,
Tarapacá. In order to attain high conversion in short time reaction, the solar
experiments were conducted during the period November to March, where the
radiation reaches highest annual intensities values in the range 720-1150 watt/
m2 (Graphic 1).
EXPERIMENTAL
General
All reagents and solvents were commercially available reagent grade.
Melting points were determined on a Stuart Scientific SMP3 apparatus and
are uncorrected. The 1H-NMR spectrum was recorded on Bruker AM-400
instrument in CDCl + DMSO-d6 The 13C-NMR spectrum was obtained at 100
MHz in CDCl3 + D3MSO-d . Chemical shifts are reported in δ ppm downfield
from TMS, and J-values ar6e given in Hertz. The mass spectrum was recorded
on a Thermo Finnigan spectrometer, model MAT 95XP. Silica gel Merck 60
(70–230 mesh) was used for preparative column chromatography and TLC
aluminum foil 60F for analytical TLC. The solar irradiation experiments
were performed in25t4he Estación Experimental de Canchones, Facultad de
Recursos Naturales Renovables, Universidad Arturo Prat in Iquique/Chile,
located in the Atacama Desert.
Photoacylation of 1,4-naphthoquinone 1 with furfural in green solvent
media.
In a previous work we reported that the solar-induced photoacylation of
1,4-naphthoquinone 1 with furfural proceeds efficiently in benzene to give
acylhydroquinone 2 in 89% yield.8 In order to explore greener conditions
to prepare 2 from naphthoquinone 1 and furfural by avoiding the use of the
toxic solvent benzene, a series of photoacylation experiments were run
in environmentally benign solvent media. According to the Pfizer solvent
selection guide,9,10 the following “preferred” solvent were selected: water,
ethyl acetate (EtOAc), isopropyl acetate (i-PrOAc), ethanol (EtOH), methanol
(MeOH), tert-butanol (t-ButOH), 1-butanol (1-ButOH), 1-propanol (1-PrOH),
Chemistry
Photoacylation of 1,4-naphthoquinone 1 with furfural in different
solvent media.
e-mail: julio.benites@unap.cl
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J. Chil. Chem. Soc., 59, Nº 2 (2014)
2-propanol (2-PrOH), acetone (DMK) and 2-butanone (MEK). The assays
were performed under standard conditions (see experimental) and the samples
were exposed to the sunlight for 30 h (5 days).
It is worth to note that precedents on the photoacylation of naphthoquinone
1 with butyraldehyde in t-BuOH and in 3:1 t-ButOH/DMK mixture, employing
artificial11,12 and solar light,13 gave the respective acylhydroquinone in 84 and
90% yield, respectively. In the light of these precedents and taking into account
the above results on the influence of the solvent media on the photoacylation to
produce acylated hydroquinone 2, we wanted to examine the effect of binary
and ternary green solvent mixtures on the photoacylation of quinone 1 with
furfural. The result of the photoacylation experiments by using a variety of
binary and ternary solvent mixtures are summarized in Table 1. The data of
these assays indicate that the photoacylation in binary t-ButOH/DMK and
ternary i-PrOAc/DMK/MEK solvent mixtures produced the acylhydroquinone
2 in 83 and 77%, respectively. Indeed, the use of t-ButOH or the binary
t-ButOH/DMK mixture appears as suitable solvent media to prepare compound
2 by solar photoacylation of 1 with furfural.
The results of the assays are summarized in Table 1. The data clearly
indicate that the efficiency of the photoacylation of 1 with furfural is strongly
dependent upon the nature of the solvent media. Thus, the photoacylation
performed in EtOAc; 2-PrOH; MEK; i-PrOAc gave the photoproduct 2 in low
to moderate yields (28-47%) however, when the photoacylation were carried
out in t-ButOH compound 2 was isolated in 80% yield. No photoacylation
reaction was detected when water, EtOH; MeOH; 1-ButOH;1-PrOH and DMK
were employed as the solvent media.
Graphic 1. Solar radiation on Canchones in the period January 2010 to
December 2012.
Photooxygenation of 1,5-dihydroxynaphthalene 3 in green solvent media.
Then we focused on developing clean preparation of juglone 4 by sensitized
photooxygenation of 1,5-dihydroxynaphthalene 3. There are several reports on
the synthesis of juglone 4 by sensitized photooxygenation of 3 in a variety
of solvents including green aqueous and ionic liquid solvents.14-16 We first
carried out in door experiments on the preparation of juglone 4 from 3 in the
“preferred” solvent media: water, EtOAc, i-PrOAc, EtOH, MeOH, t-ButOH,
1-ButOH, 1-PrOH, 2-PrOH, DMK and MEK. The photooxygenation assays,
performed using rose bengal (RB) as sensitizer and LED lamps as radiation
source, are summarized in Table 2.
Table 2. Photooxygenation of 1,5-DHN in different solvent media under
LED radiation.
Table 1. Solar photoacylation of quinone 1 with furfural in green solvent
media.
Yield
Yield
Solvent media
Solvent media
t-ButOH
(%)a
(%)a
Solvent Conversion Yield Solvent Conversion
Yield
(%)
(s)
(%)
43
77
55
62
27
44
(%)a
55
(s)
/%)
Benzene
Water
89
nr
80
nr
Water
1-ButOH
1-PrOH
2-PrOH
DMK
43
30
75
83
50
64
1-ButOH
1-PrOH
2-PrOH
DMK
EtOAc
iPrOAc
EtOH
17
49
EtOAc
i-PrOAc
EtOH
47
28
nr
nr
16
43
45
nr
64
46
MeOH
t-BuOH
83
MEK
50
MeOH
nr
MEK
37
35
Binary mixture (1:1; v/v proportion)
a) Determined on the initial and recovered amounts of precursor 3
EtOAc/2-PrOH
54
38
31
i-PrOAc/DMK
28
48
83
The data of these assays indicate that the photooxygenation of 3 in water;
EtOH and MEK solvent media yield product 4 in moderate yields (50-64%).
Better yields formation of 4 (75-83%) was achieved in MeOH; 1-PrOH and
2-PrOH solvent media. Based on the conversion of 3 versus yield formation
of 4, the photooxygenation in EtOH is the optimal experimental condition to
prepare juglone 4 by LED lamps.
EtOAc/EtOHb
DMK/EtOAcb
EtOAc/MEK
t-ButOH/DMK
Ternary mixture (1:1:1; v/v/v proportion)
Based on the in door photooxygenation experiment of compound 3 “on
water” and considering that water is a desirable solvent for chemical reactions
for reasons of cost, safety, and environmental concerns, the out door sensitized
photooxygenation of compound 3 on water was examined. The reaction was
carried out under standard condition to give juglone 4 in good yield (81%)
but low precursor conversion was observed (27%). Interestingly, when the
photooxygenation of compound 3 was performed on water, in the presence
of 5% mol of sodium dodecyl sulfate to facilitate the transfer of the lipophilic
product 4 out of the aqueous medium, high precursor conversion was observed
albeit the product 4 was isolated in moderate yield (39%).
DMK/2-PrOH/1-
ButOH
29
i-PrOAc/DMK/1-ButOH
29
EtOAc/PrOH/t-ButOH
EtOAc/PrOH/EtOH
21
18
i-PrOAc/DMK/MEK
77
25
i-PrOAc/EtOAc/t-BuOH
EtOAc/2-PrOH/t-
ButOH
17
33
i-PrOAc/EtOAc/MEK
41
21
i-PrOAc/DMK/t-
ButOH
i-PrOAc/2-PrOH/t-
BuOH
a) Isolated by column chromatography
b) 3:1; v/v proportion
nr: no reaction
CONCLUSION
In
summary,
we
have
developed
greener
access
to
furoylnaphthohydroquinone 2 and juglone 4 through photoacylation and
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J. Chil. Chem. Soc., 59, Nº 2 (2014)
photooxygenation procedures induced by solar light. Compound 2 was
prepared in 80 and 83% yield by solar photo Friedel Crafts acylation of
1,4-naphthoquinone 1 with furfural in t-ButOH and in the binary1:1 t-ButOH/
MEK solvent media. The use of the ternary 1:1:1 i-PrOAc/DMK/MEK solvent
mixture also provides green preparation of compound 2 (77%).
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The photooxygenation of 1,5-dihydroxynaphthalene 3 sensitized with
Rose Bengal conducted in EtOH; 1-PrOH and 2-PrOH solvent media provides
clean and efficient access to juglone 4 (75-83%). The photooxygenation of 3
performed “on water” and in water containing sodium dodecyl sulfate yield
juglone 4 in 81 and 39% yield, respectively.
10. R. K. Henderson, C. Jiménez-González, D. J. C. Constable, S. R. Alston,
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ACKNOWLEDGEMENTS
The authors thank Pilar Díaz, for their excellent technical assistance. This
work was supported by grants from Fondo Nacional de Ciencia y Tecnología
(Grant No. 1100376 and 1120050)
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