Microphotochemistry using 5-mm light-emitting diodes: Energy-efficient photooxidations

Article abstract of DOI:10.1055/s-0031-1289764

Commercial, inexpensive 5-mm milliwatt light-emitting diodes are effective sources for batch microphotochemical oxidations. Using limited quantities of singlet oxygen, these oxidations are atom economical and therefore useful for labeling experiments with rare isotopes. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289764

2560▌
PAPER
paper
Microphotochemistry Using 5-mm Light-Emitting Diodes: Energy-Efficient
Photooxidations
Synthesis of Endoperoxides by LED Microphotooxidation
John M. Carney, Reagan J. Hammer, Martin Hulce,* Chad M. Lomas, Dayna Miyashiro
Department of Chemistry, Creighton University, 2500 California Plaza, Omaha, NE 68178-0323, USA
Fax +1(402)2805737; E-mail: mhulce@creighton.edu
Received: 29.02.2012; Accepted: 07.03.2012
the use of sensitizer dyes,25 for example, methylene blue,
Abstract: Commercial, inexpensive 5-mm milliwatt light-emitting
Rose Bengal, or tetraphenylporphyrin.
diodes are effective sources for batch microphotochemical oxida-
tions. Using limited quantities of singlet oxygen, these oxidations
are atom economical and therefore useful for labeling experiments
with rare isotopes.
O
1O2
O
a
Key words: photooxidation, arenes, peroxides, photoreactors,
light-emitting diodes
1O2
O
O
b
c
Oxidations are among the most ubiquitous of chemical
transformations: thousands of methods, some of great his-
torical significance in organic synthesis, exist.1 Many of
these employ well-known, reliable, readily available re-
agents such as the Jones reagent,2 pyridinium chlorochro-
mate,3 potassium permanganate,4 hypochlorites,5
hydrogen peroxide,6 and osmium tetraoxide.7 Molecular
oxygen is among the simplest of oxidizing reagents. It is
responsible for inadvertent aerial oxidation of aldehydes8
and for autooxidative processes9 some of which, like the
cumene process10 to prepare phenol, are industrially sig-
nificant.
O
1O2
OH
Scheme 1 a) [4+2] Cycloaddition of 1O2 with a conjugated diene; b)
[2+2] cycloaddition of 1O2 with an alkene; c) ene reaction of the allyl-
ic positions of an alkene with 1O2
A variety of biochemical roles have been identified for
this reactive oxygen species (ROS).26 It is generated in
many biological systems, including peroxidase and li-
pogenase oxidations,27 the decomposition of lipid perox-
ides,28 photosynthesis,29 plant defense,30 and spore
germination induction.31 Exceptionally toxic, it is the pri-
mary agent of photodynamic therapy.32
With an interest in studying the thermal reversion13a,22 of
photochemically generated endoperoxides using 17O
NMR spectroscopy,33 we sought a simple, high efficiency,
small-scale photochemical apparatus for the [2+4] cyclo-
addition of various conjugated alkadienes and arenes34 us-
ing near stoichiometric amounts of isotopically labeled
1O2.27b,28b,35 Standard photoreactors using immersion
wells are too large for such an application; photoreactions
run in them require careful attention to cooling of the
source and monitoring evaporation of the solvent.36 Re-
gardless, photooxidations typically bubble excess oxygen
through the reaction medium. This can lead to significant
solvent loss37 even when the oxygen stream is solvent-
presaturated.
In its ground state, molecular oxygen exists as a triplet. It
has two low-lying excited states, the first excited singlet
delta (1Δg) and second excited singlet sigma (1Σg) states,
responsible for unique oxidative chemical properties.11,12
Most common among these are three characteristic hydro-
carbon addition reactions: [2+4] cycloadditions13 of
1
O2[1Δg] (hereafter O2) to produce endoperoxides, [2+2]
cycloadditions11c,14 to produce 1,2-dioxetanes, and
Schenck ene reactions15 to produce allylic hydroperoxides
(Scheme 1).
Singlet oxygen may be produced thermally or photochem-
ically. Well-known thermal methods include production
from hydrogen peroxide and hypochlorite16 or molyb-
date,17 calcium peroxide diperoxohydrate,18 ozone and its
derivatives,19 and hypervalent iodine compounds,20 and
by decomposition of dioxetanes21 and arene endoperox-
ides.13a,22 Recently, its formation from the fragmentation
of certain 1,1-dihydroperoxides has been reported.23 Di-
rect photochemical generation24 of singlet oxygen from
triplet oxygen is inefficient, the transition being formally
forbidden. Consequently, efficient preparation requires
1
Dye-sensitized production of O2 with methylene blue
uses visible light, so use of an external source has been
demonstrated to be effective. For example, using a 5-mL
round-bottom flask equipped with a magnetic stirrer bar,
an ice water cooled condenser, and an oxygen inlet capil-
lary tube running down the condenser into the flask, ca. 40
mg (240 μmol) of 1,4-dimethylnaphthalene in a 0.3 mol%
solution of methylene blue in dichloromethane (4 mL)
could be completely photooxidized over 72 hours in a
3 °C cold room when a 500-W incandescent lamp, IR-fil-
SYNTHESIS 2012, 44, 2560–2566
Advanced online publication: 24.04.2012
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DOI: 10.1055/s-0031-1289764; Art ID: SS-2012-C0207-ST
© Georg Thieme Verlag Stuttgart · New York

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Synthesis of Endoperoxides by LED Microphotooxidation
2561
tered by passing its output through a 10-cm recirculating multiwatt LED arrays have been used in photodynamic
refrigerated water wall, was projected onto the flask therapy32b,40 and various microfluidic and batch photore-
(Scheme 2). The inconvenience of adding dichlorometh- actors.41 Use of standard 5-mm milliwatt LEDs is more
ane (2 mL) to the flask every 4 hours to compensate for limited;42 however, their inherently narrow emissions
evaporation and the nonstoichiometric use of oxygen (FWHM ≤30 nm), low thermal output, narrow viewing
make this approach to endoperoxide synthesis unappeal- angles (30° or less), availability of emission frequencies
ing. Thus, attention was turned to the use of static, pres- from the UV into the near-IR, and low cost make them
surized atmospheres of oxygen and cooler sources.
very attractive for small-scale investigations.
Sources therefore were constructed from three 5-mm, nar-
row (8–30°) viewing angle LEDs of the same peak emis-
sion wavelength, bundled into a 1.5 × 11 cm piece of glass
tubing. Power was provided with a 12-V DC power sup-
ply or a 9-V DC battery. The total power consumption of
the sources ranged from 240 to 375 mW. Using the previ-
ously described reaction conditions for the photooxida-
500 W WX
O
O2
+
O
MB, CH2Cl2
3 °C, 72 h
excess
Scheme 2 WX = tungsten halogen lamp; MB = methylene blue
tion of 9,10-dimethylanthracene in
a
hypo-vial,
endoperoxide formation as a function of LED source peak
emission wavelength was investigated by monitoring the
relative concentrations of the starting arene and product
Using 9,10-dimethylanthracene, which undergoes photo-
oxidation much more rapidly than 1,4-dimethylnaphtha-
lene, the 5-mL flask and condenser were replaced with a
10-mL hypo-vial equipped with a stirrer bar. This hypo-
vial was charged with ca. 45 μmol of arene and was
crimped shut using a silicone septum stopper and alumi-
num seal with a tear-away opening. After the tear-away
opening was removed, a 14/20 septum stopper was placed
on top of the sealed hypo-vial to insure a gas-tight seal.
Then, the hypo-vial was wrapped in aluminum foil to ex-
clude light, and was charged with a 0.3 mol% solution of
methylene blue in dichloromethane (5 mL). After two
–78 °C freeze–aspirator pump–N2 purge–thaw cycles, the
hypo-vial was evacuated at –78 °C, then injected with 5–
15 mL of oxygen, corresponding to a 2.2–10-fold molar
excess. After the aluminum foil was removed, the con-
tents of the hypo-vial were stirred rapidly while irradiated
with the IR-filtered 500-W source as before. After 20–25
minutes, analysis by silica gel TLC using petroleum ether
as eluent indicated no starting arene remained (Rf = 0.63);
the corresponding endoperoxide was the only observable
product. No endoperoxide formation was observed if the
hypo-vial remained wrapped in foil.
1
endoperoxide by H NMR spectroscopy (methyl reso-
nances at δ 3.15 and 2.19 ppm, respectively). Two sourc-
es, those with peak emission wavelengths at 627 and 405
nm, provided ≥98% conversion into endoperoxide (Figure
1). With the former source, essentially all of the incident
light is absorbed by the methylene blue photosensitizer,
allowing for very efficient 1O2 production. With the latter
source, 9,10-dimethylanthracene rather than methylene
blue acts as photosensitizer43 (Figure 2); thus, endoperox-
ide was produced with equal efficiency when the reaction
was performed without methylene blue.
Having established that static, pressurized atmospheres of
oxygen were sufficient for small-scale endoperoxidation,
it was clear that use of a bulky source requiring aggressive
IR filtering was not ideal. These reasons supported the as-
sessment: failure of the IR filter would lead to dangerous
Figure 1 Methylene blue sensitized photooxidation of 9,10-dimeth-
heating of a small, pressurized, closed system; safety ylanthracene as a function of LED source wavelength
aside, any heating of the reaction vessel by the source
would be counterproductive for the synthesis of thermally
The superior energy efficiency of these LED sources was
labile endoperoxides, and the total energy input required
notable: compared with a 250-watt incandescent source,
for this type of source significantly offsets the atom econ-
the 627-nm LED source provided an 8700-fold increase in
omy gained by the use of near stoichiometric amounts of
efficiency of watts used per unit conversion (Table 1).
oxygen. Knowing that even relatively cool light sources
With an atom-economical microphotochemical LED ap-
produce thermal emissions sufficient to make them unsat-
paratus now available, three classes of dienes were as-
isfactory for stand-alone use to prepare some endoperox-
sayed to determine its general utility (Table 2). Arenes
ides,38 our search for an effective alternative source
and α-terpinene provided good to excellent yields of the
concentrated on highly energy-efficient, milliwatt light-
corresponding endoperoxides over times ranging from 23
emitting diodes (LEDs) with narrow viewing angles.
minutes to 24 hours (entries 1–5). Room-temperature pho-
Multiwatt LED sources have found application in photo-
tooxidation of cyclone (2,3,4,5-tetraphenyl-2,4-cyclopen-
chemistry: a commercial photoreactor has appeared,39 and
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2560–2566

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J. M. Carney et al.
PAPER
Table 2 627-nm LED Photooxidations in 0.3 mol% Methylene Blue
Solution in Dichloromethane
Entry Substrate
Time
(min)
Product
Yield
(%)
>98,
84a
O
1
23
23
O
O
Ph
Ph
O
>98,
86a
2
Ph
Ph
O
3
4
180
92
96
O
O
O
1440
5
6
23
23
81
89
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
O
O
Ph
Figure 2 Solid lines, LED emission spectra; dashed lines, absorbance
spectra
Ph
O
Ph
Ph
Ph
Ph
Ph
Ph
Table 1 Source Energy Input in watts vs Percent Conversion
65b
98c
7
8
30
Ph
Ph
CHO
Energy input
3 × 627 nm LED Incandescent WX
Ph
O
O
O
HO
Source
0.36
250.0
1380
IR filter
a Without methylene blue; 405 nm LED source.
b Z/E = 4.7:1.
Pump
5.5
1400.0
1655.5
51
c Reaction run in MeOH.
Haake K20 bath
Total watts
% Conversion
watts/% conversion
0.36
98
0.37
dienone46 provided a single product upon photooxidation,
presumably (Z)-2,3-dimethyl-1,4-diphenyl-2-butene-1,4-
dione. On the other hand, 2,5-diethyl-3,4-diphenyl-2,4-
cyclopentadienone47 provided a complex mixture of prod-
ucts, apparently from competing endoperoxidation and
ene reactions. In an attempt to generate singlet oxygen by
direct excitation from the triplet ground state, a source
consisting of three 5-mm, 30° viewing angle, 1300-nm,
near-IR LEDs was used to irradiate a 56.2-μmol sample of
recrystallized 9,10-dimethylanthracene plus oxygen (15
mL, 670 μmol) in dichloromethane (5 mL) for 48 hours at
3246.1
tadienone) provided a transient endoperoxide which
subsequently decarbonylated to provide (Z)-1,2,3,4-tetra-
phenyl-2-butene-1,4-dione (entry 6). The analogous fu-
ran, 2,3,4,5-tetraphenylfuran, yielded the same 2-butene-
1,4-dione,44 but as a mixture of E- and Z-isomers (entry 7).
Modifying the photooxidation of furfural37,45 to provide 5-
hydroxy-2(5H)-furanone so as to be amenable to the mi-
croscale proved to be straightforward: the lactone was
produced in very good yield (entry 8).
1
3 °C. H NMR spectroscopy indicated 1.5% conversion
In other, preliminary work, it was discovered that similar
to cyclone, 3,4-dimethyl-2,5-diphenyl-2,4-cyclopenta-
into the endoperoxide.
Synthesis 2012, 44, 2560–2566
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Synthesis of Endoperoxides by LED Microphotooxidation
2563
va spectrometer at 300, 75, and 40.7 MHz, respectively. IR spectra
were acquired on a Thermo Avatar 370 spectrometer equipped with
a Pike Technologies MIRacle single reflection ZnSe ATR sampling
accessory, and were ATR-corrected after acquisition. EI mass spec-
tra (70 eV) were obtained using an Agilent 6850/5973 GC/MSD
system. MALDI mass spectra were acquired with an Applied Bio-
systems DE Voyager Pro mass spectrometer. HPLC was performed
on a Hewlett-Packard 1100 isocratic chromatograph using a
50 × 4.6 mm Alltech Econosphere 3-μ, 60-Å silica column; detec-
tion was at 254 nm. GC/MS used a 30-m Alltech Econocap EC-5
column with a helium gas flow rate of 1 mL/min; the injector tem-
perature was 250 °C, and the oven temperature program 60 °C (3
min), 10 °C/min (18 min), 240 °C (9 min). Analytical TLC was per-
formed using Analtech silica gel GHLF 250-μm, 2.5 × 7.5 cm
plates, visualized by UV light after development.
Finally, but not unexpectedly, the optimized conditions
for microphotochemical oxidation were equally effective
when 40 atom% 17O2 (ca. 4 mol equiv) was used to form
the endoperoxides of 9,10-diphenylanthracene, 1,4-di-
methylnaphthalene, and 1,8-dimethylnaphthalene.48
These 17O-labeled peroxides had robust 17O NMR spectra
(Table 3).
Table 3 17O NMR Endoperoxide Chemical Shifts
δ (ppm)a
Endoperoxide
Linewidth (KHz)
Ph
9,10-Dimethylanthracene 9,10-Endoperoxide52
O
O
107.7
4.7
9,10-Dimethylanthracene (10.3 mg, 49.9 μmol) was sealed in an
aluminum foil wrapped, magnetic stirrer bar equipped, 10-mL
hypo-vial. The vial was charged with 27 μM methylene blue in
CH2Cl2 (5 mL). After two –78 °C freeze–aspirator pump–N2 purge–
thaw cycles, O2 (12 mL, ca. 0.5 mmol, 10 equiv) was injected into
the vial using a gas-tight syringe. The foil was removed and the con-
tents of the reaction vial were stirred rapidly at 3 °C as the vial was
irradiated with three 125-mW, 627-nm LEDs. After 20–25 min, the
vial was vented by inserting a syringe needle through the septum.
The septum was removed and the contents of the vial were filtered
through a Pasteur pipet containing a 1–2-cm plug of neutral chro-
matographic alumina into a tared, 25-mL round-bottom flask. The
alumina plug was washed with CH2Cl2 (3–5 × 1 mL); these wash-
ings were combined with the filtrate. Concentration by rotary evap-
oration afforded 9,10-dimethylanthracene 9,10-endoperoxide as a
white solid containing no 9,10-dimethylanthracene (Rf = 0.63)
when analyzed by TLC (petroleum ether); yield: 11.8 mg (99%).
Ph
O
O
300.2
287
1.5
1.4
O
O
a Relative to H2O.
In conclusion, commercial, inexpensive 5-mm milliwatt
light-emitting diodes are effective sources for batch mi-
crophotochemical oxidations. Using limited quantities of
singlet oxygen, these oxidations are atom economical and
therefore useful for isotopic labeling. Extensions to other
photochemical reactions using gaseous reactants, such as
[2+2] cycloadditions of ethane to conjugated ketones,36b
are under investigation.
IR: 3041 (w), 2983 (w), 2935 (w), 1463 (m), 1378 (m), 756 (s) cm–1.
1H NMR (CDCl3): δ = 7.44 (m, 4 H), 7.31 (m, 4 H), 2.19 (s, 6 H).
13C NMR (CDCl3): δ = 141.11, 127.64, 120.91, 79.84, 13.95.
MS (MALDI): m/z = 239.12 [M + H+].
Similarly, a sealed 10-mL hypo-vial containing 9,10-dimethylan-
thracene (9.4 mg, 45.6 μmol), CH2Cl2 (5 mL), and O2 (12 mL, ca.
0.5 mmol, 11 equiv) was stirred rapidly at 3 °C and irradiated with
three 80-mW, 405-nm LEDs for 20–25 min. Workup afforded 9,10-
dimethylanthracene 9,10-endoperoxide as a white solid in greater
than 98% purity, as determined by 1H NMR analysis; yield: 9.1 mg
(84%).
Cyclohexane, CH2Cl2, CHCl3, MeCN, benzene, EtOAc, petroleum
ether, MeOH, EtOH, acetone, 9,10-dimethylanthracene, methylene
blue, 1,4-dimethylnaphthalene, α-terpinene, neutral alumina, silica
gel, and 40 atom% 17O2 were used as received. Anthracene was re-
crystallized twice from cyclohexane before use. Furfural was dis-
tilled before use. 9,10-Diphenylanthracene was prepared from 9,10-
dibromoanthracene,49 2,3,4,5-tetraphenyl-2,4-cyclopentadienone
from benzil and dibenzyl ketone,50 and 2,3,4,5-tetraphenylfuran
from 2-bromo-2-phenylacetophenone.51 Photooxidations were run
in magnetic stirrer bar equipped, 10-mL, silicone septa sealed, 20-
mm crimp-top glass vials. Standard 250- and 500-watt WX incan-
descent sources were used in conjunction with an IR filter made
from a 27 × 27 × 10 cm glass tank filled with circulating water
cooled to 3 °C with a copper heat-exchanging coil attached to a
Thermo Haake K20 refrigerated recirculating bath. The distance
from source to reaction vessel was 30 cm. LED sources were con-
structed of LEDs purchased from Super Bright LEDs, Inc. or Thor
Scientific Products and an 800-mW, 12-V DC power supply. A typ-
ical source consisted of three narrow viewing angle LEDs of the
same emission wavelength inserted in a 1.5 × 11 cm piece of glass
tubing so that the LED lenses were flush with the end of the tubing.
The distance from source to reaction vessel was 0 cm. 3 °C reac-
tions were performed in a cold room in the dark. Room temperature
reactions were run under a double thickness of sueded black cloth.
1H, 13C, and 17O NMR spectra were recorded on a Varian Unity Ino-
9,10-Diphenylanthracene 9,10-Endoperoxide18,35a,b,53
In a manner similar to the preparation of 9,10-dimethylanthracene
9,10-endoperoxide, a sealed 10-mL hypo-vial containing 9,10-di-
phenylanthracene (10.4 mg, 31.5 μmol), 27 μM methylene blue in
CH2Cl2 (5 mL), and O2 or 40 atom% 17O2 (12 mL, ca. 0.5 mmol, 16
equiv) was stirred rapidly at r.t. and irradiated with three 125-mW,
627-nm LEDs for 20–25 min. Workup afforded 9,10-diphenylan-
thracene 9,10-endoperoxide as a white solid in 97% purity, as deter-
mined by 1H NMR analysis; yield: 11.6 mg (ca. 100%).
HPLC: tR = 7.2 min (CH2Cl2–cyclohexane, 2:8; 0.5 mL/min).
IR: 3074 (w), 1599 (w), 1494 (m), 1458 (m), 920 (m), 764 (s), 744
(s), 703 (m) cm–1.
1H NMR (DMSO-d6): δ = 7.75–7.66 (m, 4 H), 7.66–7.58 (m, 6 H),
7.34–7.28 (m, 4 H), 7.12–7.04 (m, 4 H).
13C NMR (CDCl3): δ = 140.49, 133.25, 128.61, 128.53, 127.91,
127.80, 123.76, 84.34.
17O NMR (CDCl3): δ = 107.7.
MS (MALDI): m/z = 363.18 [M + H+].
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2560–2566

2564
J. M. Carney et al.
PAPER
Similarly, a sealed 10-mL hypo-vial containing 9,10-diphenylan-
thracene (12.6 mg, 38.1 μmol), CH2Cl2 (5 mL), and O2 (12 mL, ca.
0.5 mmol, 13 equiv) was stirred rapidly at 3 °C and irradiated with
three 80-mW, 405-nm LEDs for 20–25 min. Workup afforded 9,10-
diphenylanthracene 9,10-endoperoxide as a white solid in 98% pu-
rity, as determined by 1H NMR analysis; yield: 11.9 mg (86%).
methylene blue in CH2Cl2 (5 mL), and O2 (12 mL, ca. 0.5 mmol,
11.2 equiv) was stirred rapidly at r.t. and irradiated with three 125-
mW, 627-nm LEDs for 20–25 min. Workup afforded (Z)-1,2,3,4-
tetraphenyl-2-butene-1,4-dione as a white solid in greater than 98%
purity, as determined by 1H NMR analysis; yield: 15.4 mg (89%).
Mp 204–206 °C (Lit.58 210.5–211.5 °C).
Anthracene 9,10-Endoperoxide54
TLC: Rf = 0.54 (petroleum ether–EtOAc, 9:1).
In a manner similar to the preparation of 9,10-dimethylanthracene
9,10-endoperoxide, a sealed 10-mL hypo-vial containing anthra-
cene (17.9 mg, 0.10 mmol), 40 μM methylene blue in CH2Cl2 (5
mL), and O2 (15 mL, ca. 0.67 mmol, 6.7 equiv) was stirred rapidly
at 3 °C and irradiated with three 125-mW, 627-nm LEDs for 3 h.
Workup afforded anthracene 9,10-endoperoxide as a white solid in
greater than 98% purity, as determined by 1H NMR analysis; yield:
19.3 mg (92%).
IR: 3062 (w), 2920 (w), 2850 (w), 1660 (s), 1596 (m), 1580 (w),
1262 (s), 695 (s) cm–1.
1H NMR (CDCl3): δ = 7.86 (m, 4 H), 7.42 (tt, J = 7.4, 2.2 Hz, 2 H),
7.31 (tt, J = 7.8, 2.5 Hz, 4 H), 7.18 (s, 10 H).
13C NMR (CDCl3): δ = 197.18, 144.82, 136.66, 135.53, 133.24,
130.28, 130.10, 128.91, 128.63, 128.55.
MS (MALDI): m/z = 389.13 [M + H+].
TLC: Rf = 0.22 (benzene–petroleum ether, 2:1).
IR: 3046 (w), 2963 (w), 1462 (w), 769 (s), 752 (s), 720 (m) cm–1.
(EZ)-1,2,3,4-Tetraphenyl-2-butene-1,4-dione
In a manner similar to the preparation of (Z)-1,2,3,4-tetraphenyl-2-
butene-1,4-dione, a sealed 10-mL hypo-vial containing 2,3,4,5-tet-
raphenylfuran (32.4 mg, 87.0 μmol), 29 μM methylene blue in
CH2Cl2 (5 mL), and O2 (15 mL, ca. 0.67 mmol, 7.7 equiv) was
stirred rapidly at r.t. and irradiated with three 125-mW, 627-nm
LEDs for 30 min. Workup afforded (EZ)-1,2,3,4-tetraphenyl-2-bu-
tene-1,4-dione (32.3 mg) as a white solid in a Z/E ratio of 4.7:1, as
1H NMR (CDCl3): δ = 7.43–7.40 (m, 4 H), 7.27–7.24 (m, 4 H), 6.02
(s, 2 H).
13C NMR (CDCl3): δ = 138.30, 128.19, 123.86, 79.64.
MS (MALDI): m/z = 211.02 [M + H+].
1,4-Dimethylnaphthalene 1,4-Endoperoxide35a,b,55
1
determined by H NMR and HPLC analyses [HPLC: tR = 2.6 (E),
In a manner similar to the preparation of 9,10-dimethylanthracene
9,10-endoperoxide, a sealed 10-mL hypo-vial containing 1,4-di-
methylnaphthalene (26.4 mg, 0.17 mmol), methylene blue (1.4 mg,
4.4 μmol, 2.6 mol%), CH2Cl2 (5 mL), and O2 or 40 atom% 17O2 (15
mL, ca. 0.67 mmol, 3.9 equiv) was stirred rapidly at 3 °C and irra-
diated with three 125-mW, 627-nm LEDs for 24 h. Crude product
(46.8 mg) was recovered as a white solid after workup at 3 °C. 1H
NMR analysis indicated 97% conversion into 1,4-dimethylnaphtha-
lene 1,4-endoperoxide.
3.2 (Z) min (EtOAc–cyclohexane, 7.7:92.3; 0.5 mL/min)]. The
crude product was recrystallized (EtOH–H2O) to give the product as
a white solid, with no change in the ratio of diastereomers; yield:
21.9 mg (65%).
5-Hydroxy-2(5H)-furanone37,45
In a manner similar to the preparation of 9,10-dimethylanthracene
9,10-endoperoxide, a sealed 10-mL hypo-vial containing furfural
(41.2 mg, 0.42 mmol), methylene blue (1.3 mg, 4.1 μmol, 1 mol%),
MeOH (5 mL), and O2 (15 mL, ca. 0.67 mmol, 1.6 equiv) was
stirred rapidly at r.t. and irradiated with three 125-mW, 627-nm
LEDs for 23 h. The contents of the hypo-vial were concentrated by
rotary evaporation, then taken up in acetone (5 mL). The acetone so-
lution was filtered through a Pasteur pipet containing a 1–2-cm plug
of silica gel into a tared, 25-mL round-bottom flask. The silica gel
plug was washed with acetone (3 × 1 mL); these washings were
combined with the filtrate. Concentration by rotary evaporation af-
forded crude 5-hydroxy-2(5H)-furanone (46.3 mg) as a clear yellow
liquid in greater than 98% purity, as determined by 1H NMR analy-
sis.
TLC: Rf = 0.11 (benzene–petroleum ether, 1:1).
IR: 3044 (w), 2982 (m), 2934 (w), 1459 (m), 1377 (m), 758 (s) cm–1.
1H NMR (CDCl3): δ = 7.40–7.25 (m, 4 H), 6.73 (s, 2 H), 1.93 (s, 6
H).
13C NMR (CDCl3): δ = 141.26, 139.48, 127.00, 120.37, 78.93,
16.41.
17O NMR (CDCl3): δ = 300.2.
MS (MALDI): m/z = 189.04 [M + H+].
Ascaridole18,20b,41b,d,56
1H NMR (CDCl3): δ = 7.33 (dd, J = 1.2, 5.7 Hz, 1 H), 6.30 (t,
J = 1.2 Hz, 1 H), 6.25 (dd, J = 1.2, 5.7 Hz, 1 H), 5.2–4.1 (1 H).
A sample was crystallized (CHCl3, –78 °C); mp 52–54 °C (Lit.45
52–55 °C).
In a manner similar to the preparation of 9,10-dimethylanthracene
9,10-endoperoxide, a sealed 10-mL hypo-vial containing α-terpi-
nene (16.3 mg, 0.12 mmol), 40 μM methylene blue in CH2Cl2 (5
mL), and O2 (15 mL, ca. 0.67 mmol, 5.2 equiv) was stirred rapidly
at 3 °C and irradiated with three 125-mW, 627-nm LEDs for 20–25
min. Workup afforded ascaridole as a clear, colorless liquid; yield:
16.3 mg (81%).
Acknowledgment
GC: tR = 10.4 min; TLC: Rf = 0.50 (petroleum ether–EtOAc, 95:5).
Funding from the Creighton University Department of Pathology
and the Creighton University Graduate School is gratefully ack-
nowledged. James T. Fletcher, Robert C. Allen, and Ahsan U. Khan
are thanked for valuable insights.
IR: 3051 (w), 2965 (s), 2932 (s), 2877 (w), 1470 (w), 1451 (m),
1378 (m), 729 (m), 697 (m) cm–1.
1H NMR (CDCl3): δ = 6.52 (d, J = 8.7 Hz, 1 H), 6.44 (d, J = 8.7 Hz,
1 H), 2.06 (m, 2 H), 1.95 (m, 1 H), 1.55 (apparent d, J = 9.9 Hz, 2
H), 1.40 (s, 3 H), 1.03 (d, J = 7.2 Hz, 6 H).
13C NMR (CDCl3): δ = 136.65, 133.31, 80.04, 74.61, 32.38, 29.77,
25.85, 21.65, 17.48, 17.40.
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