The solar-chemical photo-Friedel-Crafts heteroacylation of 1,4-quinones

Article abstract of DOI:10.1016/j.tetlet.2010.11.149

Photochemical reactions between 1,4-benzo- and 1,4-naphthoquinone and several heteroaromatic carbaldehydes were investigated under solar irradiation conditions. These reactions gave the corresponding heteroacylated hydroquinones in the range 71%-92% yield

Full text of DOI:10.1016/j.tetlet.2010.11.149

Tetrahedron Letters 52 (2011) 609–611
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Tetrahedron Letters
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The solar-chemical photo-Friedel–Crafts heteroacylation of 1,4-quinones
Julio Benites a,b, David Rios a,b, Pilar Díaz a, Jaime A. Valderrama b,c,
⇑
a Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat, Casilla 121, Iquique, Chile
b Instituto de EtnoFarmacología (IDE),Universidad Arturo Prat, Casilla 121, Iquique, Chile
c Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago, Chile
a r t i c l e i n f o
a b s t r a c t
Article history:
Photochemical reactions between 1,4-benzo- and 1,4-naphthoquinone and several heteroaromatic car-
baldehydes were investigated under solar irradiation conditions. These reactions gave the corresponding
heteroacylated hydroquinones in the range 71%–92% yield.
Received 8 October 2010
Revised 23 November 2010
Accepted 29 November 2010
Available online 4 December 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Photo-Friedel–Crafts acylation
Heteroacylhydroquinones
Solar light
Photochemistry
Heterocycles
Acylated 1,4-quinones, easily prepared by oxidation of the cor-
responding acylhydroquinones, are valuable precursors of a variety
of natural1–4 and synthetic compounds endowed with a range of
biological properties.5–13 Acylhydroquinones are most commonly
prepared via Friedel–Crafts acylation or Fries-rearrangement.14–19
Although the yields are in general moderate to good, these classical
methods involve the use of hazardous environmental substances
and suffer of limitations regarding the use of precursor containing
acid-labile functional groups because they are carried out under
strong acid conditions.
Our continuous interest to extend the synthetic utility of
acyl-1,4-benzoquinones to new biological active quinones7–13
and precedents on photoacylation of 1,4-quinones with alde-
hydes,20–29 in particular those reported by Klinger,20 Oelgemöller
and Mattay,25–27 on the use of green photochemistry using natu-
ral sunlight to the Friedel–Crafts acylation of 1,4-quinones with
carbocyclic aldehydes, led us to study the application of the solar
chemistry to the synthesis of heteroacylhydroquinones from
1,4-benzo- and 1,4-naphthoquinones 1 and 2, and various het-
eroaromatic aldehydes. It is important to point out that the syn-
thesis of heteroacylhydroquinones has received relatively little
attention and there is only one report on the preparation of
some members such as 3 and 4. The access to these compounds
proceeds by acylation of hydroquinone dimethylether with the
corresponding carboxylic acid induced with polyphosphoric acid.
Further demethylation of the dimethoxyketones with boron
tribromide followed by oxidation affords the corresponding
heteroacylhydroquinones.30,31
OH O
OH O
S
O
OH
OH
3
4
We firstly explored the photolysis of 1,4-benzoquinone 1 in the
presence of 7.5 equiv of furan-2-carbaldehyde in order to inhibit
competing photodimerizations of the quinone26 in benzene solu-
tion, and also containing a catalytic amount of benzophenone to
facilitate the eventual photoacylation.32
Solar irradiation was employed to induce the acylation and
the reaction course was daily monitored by thin layer chromatog-
raphy (light petroleum 40–60/ethyl acetate). After 30 h of light
irradiation (six days) the reaction went to completion to give
heteroacylhydroquinone 3 as the sole product in 88% isolated yield
(Scheme 1).
Several trials of acylation reaction of benzoquinone 1 with
furan-2-carbaldehyde were also carried out in the absence of
O
O
OH
sun, 30 h
+
O
O
O
N2, benzene
O
OH
1
3
⇑
Corresponding author. Tel.: +56 2 68644320; fax: +56 2 6864744.
E-mail address: jvalderr@uc.cl (J.A. Valderrama).
Scheme 1. Photoacylation of 1 with furan-2-carbaldehyde.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.149

610
J. Benites et al. / Tetrahedron Letters 52 (2011) 609–611
benzophenone, which indicates that the use of this compound does
not influence the yield of the phothoacylation.
unique products, were detected after 48 h of irradiation. However,
partial conversion of quinone 1 and 2 (46% and 22%, respectively)
to their photoproducts were observed after ten days of irradiation.
Photoproducts 3 and 8 were isolated in 55% and 88% yields, respec-
tively. As in the solar experiments, the presence of catalytic
amounts of benzophenone did not improve the yields of the pho-
thoacylation reactions. Although the above experiments demon-
strate the feasibility of the photoacylation of quinones 1 and 2
with furan-2-carbaldehyde under artificial light, further experi-
ments should be carried out to improve the photoacylation conver-
sions and to know the scope of the reaction with heteroaldeydes.
In conclusion, we have described a facile, efficient, cheap and
high-yielding procedure to prepare heteroacylhydroquinones. The
reported method involves commercially available precursors and
an efficient solar photoacylation of 1,4-benzo- and 1,4-naphtho-
quinone. Our work demonstrates that the use of green photochem-
istry with sunlight is achievable for the acylation of 1,4-quinones
with heteroaromatic aldehydes. Further work is in progress to re-
place benzene by alternative solvents suitable for green chemistry.
Encouraged by this result, we set out to study the scope of this
photoacylation procedure for the synthesis of heteroacylhydroqui-
nones 4–14 and the results are collected in Table 1. In all the exam-
ined cases the heteroacylhydroquinones were obtained in good to
excellent yields. The structure of the new compounds 3–12 were
deduced from IR, 1H and 13C NMR data.
All solar experiments reported here33 were performed at the
Canchones Experimental Center in Iquique/Chile (latitude
20°26043.8000 S, 990 m above sea level), which is located in the
Atacama desert, one of the most insolate regions of the world.
In order to evaluate the photoacylation of quinones employing
an artificial irradiation source, the reactions of quinones 1 and 2
with furan-2-carbaldehyde were examined under the same
conditions employed in the solar experiments.33 Degassed reaction
mixtures were irradiated by means of 130-W UV-fluorescent
lamps and the progress of the reactions were monitored by TLC.
The presence of the corresponding photoproducts 3 and 8, as the
Acknowledgement
Table 1
We thank Fondo Nacional de Ciencia y Tecnología (Grant No.
1100376) for financial support to this study.
Solar photoacylation of 1,4-quinones with heteroaromatic carbaldehydes
Quinone
Aldehyde
Photoproduct
No
Rend.a (%)
O
OH O
O
O
References and notes
3
88
O
OH
OH O
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O
S
4
5
83
87
81
72
89
85
92
71
80
S
OH
OH O
O
O
O
S
S
O
O
OH
OH O
O
N
H
6
HN
OH
OH O
O
O
O
N
7
N
O
OH
O
OH O
O
O
8
O
O
O
OH
OH O
2
O
S
9
S
O
O
OH
OH O
O
S
10
11
12
S
O
O
OH
OH O
O
N
H
HN
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Chem. 2009, 11, 1867–1870.
O
O
OH
OH O
O
N
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a
Isolated yield.

J. Benites et al. / Tetrahedron Letters 52 (2011) 609–611
611
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1 1980, 1414–1419.
(2,5-Dihydroxyphenyl)(thiophen-3-yl)methanone (5): orange solid mp, 135–
136 °C. IR (KBr, cmꢀ1 mmax 3334 (O–H), 1581 (C@O). 1H NMR (200 MHz,
)
CDCl3) 11.74 (s, 1H, 2-OH), 8.38 (s, 1H, 5-OH), 8.32 (s, 1H, 20-H), 7.89 (m, 1H, 40-
or 50-H), 7.85 (d, 1H, J = 8.2 Hz, 3- or 4-H), 7.71 (d, 1H, J = 8.2 Hz, 4- or 3-H),
7,49 (d, 1H, J = 3.0 Hz, 50- or 40-H), 7.30 (s, 1H, 6-H). 13C NMR (50 MHz, CDCl3)
193.6, 156.0, 148.7, 140.1, 132.1, 128.1, 125.9, 124.4, 122.1, 118.5, 116.9. Anal.
Calcd for C11H8O3S: C, 59.99; H, 3.66; S, 14.56. Found: C, 59.93; H, 3.65; S,
14.17.
30. Singh, P.; Pardasani, R. T.; Prasant, A.; Pokharna, C. P.; Chaudhary, B. Pharmazie
1993, 48, 699–700.
31. Pardasani, R. T.; Pardasani, P.; Muktawat, S.; Ghosh, R.; Mukherjee, T.
Heterocycl. Commun. 1998, 4, 77–80.
32. For the mechanism of the benzophenone-initiated photoadditions of acyl
radicals to the quinone system see Refs. 23 and 24.
(1,4-Dihydroxynaphthalen-2-yl)(thiophen-3-yl)methanone (10): dark orange
33. General procedure for the synthesis of heteroaroylhydroquinones:
A
100 mL
solid mp, 159–160 °C. IR (KBr, cmꢀ1 mmax 3317 (O–H), 1580 (C@O). 1H NMR
)
benzene solution of the required quinone (1 mmol) and aldehyde (7.5 mmol),
was placed into the outer jacket of a Liebig condenser type. The solution was
bubbled with nitrogen (2 min), sealed with a septum and then irradiated for six
days (total illumination time of 30 h), under solar radiation conditions in the
range 800–1100 Watts/m2 (January–March) The solvent was evaporated under
reduced pressure and the residue was chromatographed on silica gel (3:1
petroleum ether/ethyl acetate). The starting aldehyde and the solvent were
recovered and employed in the next batches.
(400 MHz, DMSO-d6): d 13.08 (s, 1H, 1-OH), 9.87 (s, 1H, 4-OH), 8.34 (d, 1H,
J = 8.3 Hz, 5- or 8-H), 8.30 (br s, 1H, 20-H), 8.14 (d, 1H, J = 8.3 Hz, 8- or 5-H), 7.77
(m, 1H, 40- or 50-H), 7.71 (t, 1H, J = 7.6 Hz, 6- or 7-H), 7.62 (t, 1H, J = 7.6, Hz, 7-
or 6-H), 7.56 (d, 1H, J = 4.8 Hz, 50- or 40-H), 7.17 (s, 1H, 3-H). 13C NMR
(100 MHz, DMSO-d6): d 193.6, 154.7, 144.8, 140.0, 133.3, 129.4, 129.2, 128.2,
127.3, 126.5, 125.3, 123.7, 122.2, 113.0, 106.2. Anal. Calcd for C15H10O3S: C,
66.65; H, 3.73; O, 17.76; S, 11.86. Found: C, 66.78; H, 3.99; S, 11.64.
(1,4-Dihydroxynaphthalen-2-yl)(1H-pyrrol-2-yl)methanone (11): dark brown
Data of selected examples: (2,5-dihydroxyphenyl)(furan-2-yl)methanone (3):
solid mp, 169–170 °C. IR (KBr, cmꢀ1 mmax 3280 (O–H), 1579 (C@O). 1H NMR
)
orange solid mp, 125.5–126.5 °C. IR (KBr, cmꢀ1
)
m
max 3330 (O–H), 1562 (C@O).
(400 MHz, DMSO-d6+CDCl3): d 13.59 (s, 1H, 1-OH), 11.75 (br s, 1H, NH), 9.31 (s,
1H, 4-OH), 8.36 (d, 1H, J = 8.4 Hz, 5- or 8-H), 8.17 (d, 1H, J = 8.4 Hz, 8- or 5-H),
7.62 (dd, 1H, J = 7.0, 8.0 Hz, 6- or 7-H), 7.58 (s, 1H, 40- or 50-H), 7.53 (dd, 1H,
J = 7.0, 8.0 Hz, 7- or 6-H), 7.21 (br s, 1H, 30-H), 7.16 (br s, 1H, 50- or 40-H), 6.35 (s,
1H, 3-H). 13C NMR (100 MHz, DMSO-d6+CDCl3): d 218.2, 185.5, 155.0, 144.2,
129.7, 128.6, 128.1, 125.3, 125.2, 123.2, 121.7, 118.7, 111.5, 110.2, 105.6. HRMS
(M+): m/z calcd for C15H11O3N: 253.07389; found: 253.07249.
1H NMR (200 MHz, acetone-d6): d 11.45 (s, 1H, 2-OH), 8.21 (br s, 1H, 5-OH),
8.01 (dd, 1H, J = 3.6, 2.7 Hz, 40- or 50-H), 7.79 (d, 1H, J = 8.3 Hz, 3- or 4-H), 7.49
(m, 1H, 30-H), 7.12 (d, 1H, J = 8.3 Hz, 4- or 3-H), 6.80 (dd, 1H, J = 3.6, 2.7 Hz, 50-
or 40-H), 6.66 (s, 1H, 6-H). 13C NMR (50 MHz, acetone-d6): d 185.1, 157.2, 152.7,
150.2, 148.8, 125.3, 121.8, 119.4, 116.7, 116.5, 113.3. Anal. Calcd for C11H8O4:
C, 64.71; H, 3.95. Found: C, 64.80; H, 3.85.