Photochemistry in supercritical carbon dioxide. The benzophenone-mediated addition of aldehydes to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1016/S0040-4039(00)02273-5

The photo-induced addition of aldehydes to α,β-unsaturated carbonyl compounds is an effective, 'environmentally benign' method for the synthesis of 2-acyl-1,4-hydroquinones (from quinones) and 1,4-diketones (from enones). This process has been improved by eliminating benzene as a solvent and replacing it with supercritical carbon dioxide. Highest yields were obtained at higher CO₂ pressures, or with the addition of 5% t-butyl alcohol as co-solvent.

Full text of DOI:10.1016/S0040-4039(00)02273-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1415–1418
Photochemistry in supercritical carbon dioxide. The
benzophenone-mediated addition of aldehydes to a,b-unsaturated
carbonyl compounds
Ryszard Pacut,a,† Michelle L. Grimm,a George A. Krausb and James M. Tankoa,*
aDepartment of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0212, USA
bDepartment of Chemistry, Iowa State University, Ames, IA 50011, USA
Received 21 September 2000; revised 5 December 2000; accepted 7 December 2000
Abstract—The photo-induced addition of aldehydes to a,b-unsaturated carbonyl compounds is an effective, ‘environmentally
benign’ method for the synthesis of 2-acyl-1,4-hydroquinones (from quinones) and 1,4-diketones (from enones). This process has
been improved by eliminating benzene as a solvent and replacing it with supercritical carbon dioxide. Highest yields were obtained
at higher CO2 pressures, or with the addition of 5% t-butyl alcohol as co-solvent. © 2001 Elsevier Science Ltd. All rights reserved.
In 1992, Kraus and co-workers reported a general
photochemical process for the synthesis of acylhy-
droquinones, starting from the corresponding aldehyde
and quinone (Scheme 1).1 The significance of this pro-
cess is that it provides a viable, ‘environmentally
benign’ alternative2 to the Friedel–Crafts acylation
reaction (Scheme 2), which typically requires (a) the use
of corrosive acid chlorides, (b) use of strong Lewis
acids (AlCl3, TiCl4, etc.), and often (c) the use of
hazardous solvents.
A likely mechanism for this process is depicted in
Scheme 3.2 Irradiation yields the quinone triplet excited
state. Because the CꢀH bond of the formyl group is
weak (<90 kcal/mol), this hydrogen is readily
abstracted by the excited state quinone yielding radical
pair 4. Radical–radical coupling, followed by enoliza-
tion, yields 3. In instances where yields were poor,
addition of catalytic quantities of benzophenone
resulted in a dramatic improvement.3 (Details regarding
the mechanism were not reported; presumably the ben-
zophenone is serving as a sensitizer.)
Scheme 1.
Scheme 2.
Keywords: environmentally benign synthesis; supercritical fluid sol-
vent; photochemistry; Friedel–Crafts acylation.
* Corresponding author. Fax: (540) 231-3255; e-mail: jtanko@vt.edu
†
On leave from the Department of Chemistry, Agricultural Univer-
Scheme 3.
sity, Wroclaw, Poland.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02273-5

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R. Pacut et al. / Tetrahedron Letters 42 (2001) 1415–1418
Table 1. Benzophenone-mediated reaction of 1,4-benzoquinone (1) with benzaldehyde in PhH and several alcoholic co-
solvents (time: 3 days)
Solvent
Unreacted 1 (%)
Yield 3a (%)
Yield 1,4-hydroquinone (%)
PhH
19
0
0
0
36
56
19
0
13
46
0
46
60
40
0
PhH+5% MeOH
PhH+5% EtOH
PhH+5% i-PrOH
PhH+5% t-BuOH
desired coupling product. Presumably the quinone
triplet state abstracts the a-hydrogen. With t-BuOH,
which does not possess a-hydrogens, yields comparable
to those observed in PhH were observed.
From an environmental perspective, one drawback to
the Kraus procedure involves the use of benzene as a
solvent. Further gains in pollution prevention could be
realized by replacing benzene with a more ‘environmen-
tally benign’ solvent. This paper describes the use of
supercritical carbon dioxide (SC-CO2)4–7 as a viable
alternative to benzene for the Kraus photochemical
acylation process.
Finally, the reaction between benzaldehyde and 1,4-
benzoquinone was performed in SC-CO2 (Table 2).10
With t-BuOH co-solvent, the yield is nearly identical to
that observed in PhH (with 5% t-BuOH). The reaction
could be conducted without co-solvent at high SC-CO2
pressure, however, the yield was somewhat lower. (Pre-
sumably solubility is still the problem even at the higher
pressure; this could not be confirmed because our view
cell is only rated to ca. 3000 psi.)
Kraus reports that in benzene solvent, the photolysis of
benzaldehyde and 1,4-benzoquinone produces the 2-
benzoyl-1,4-hydroquinone (3a) in 60% yield.1 Under the
reported conditions of these experiments, the concen-
trations of 1,4-benzoquinone and benzaldehyde were
0.2 and 1.4 M, respectively. Because SC-CO2 is non-
polar, such high concentrations of these polar sub-
strates could not be achieved. Hence, initial
experiments were designed to repeat the Kraus experi-
ments in benzene, but at significantly lower concentra-
tions. The following conditions proved optimal,
resulting in a 64% yield of 3a: 0.1 M benzaldehyde,
0.015 M 1,4-benzoquinone, and 0.015 M benzophenone
(mediator); irradiation was accomplished using a Rayo-
net photochemical reactor (254 nm). Use of lower
benzophenone concentrations resulted in diminished
yields. These results demonstrate that it is feasible to
conduct this reaction at significantly lower reagent con-
centrations, as is needed for transfer of this chemistry
to SC-CO2 solvent.
Kraus reports that the reaction of butyraldehyde (2b)
and benzoquinone in PhH produces the corresponding
2-acyl-1,4-hydroquinone (3b) in 82% yield.1 A solubility
check revealed that in SC-CO2, butyraldehyde is soluble
(0.15 M, 1200 psi and above), although the reaction
product 3b is not. Our results under dilute conditions
similar to above (in PhH with 5% t-BuOH and in
SC-CO2 under various conditions) are summarized in
Table 3.
The results in Table 3 demonstrate that in SC-CO2
solvent, the product yield increases with increasing
pressure. In the best case (SC-CO2 with 5% t-BuOH),
the yield is identical to that observed in PhH solvent.
The effect of pressure and/or co-solvent on reaction
yield suggests solubility problems at lower pressures.
Indeed, visual observations reveal that the reaction
mixture is only partly soluble in SC-CO2 at low pres-
sure, but becomes more soluble at higher pressures (or
in the presence of t-BuOH).
Utilizing a view cell, the solubility of the reactants in
SC-CO2 was checked at 50°C. Generally, the solubility
of polar solutes diminishes at lower CO2 pressures.8,9
At pressures of 1200 psi (just above the critical pres-
sure) and at 2500 psi, benzophenone and benzaldehyde
were observed to be fully soluble in SC-CO2. However,
1,4-benzoquinone was not fully soluble, even at the
higher pressure. Solubility of polar materials in SC-CO2
can be improved either by (a) increasing the pressure
(and also temperature), or (b) via the use of a co-sol-
vent to increase the polarity of the medium.8,9 Alcohols
are frequently used as co-solvents to improve solubility
of polar solutes in SC-CO2 solvent in supercritical fluid
extractions, and were tested as co-solvents for this
reaction; preliminary experiments utilized benzene as a
solvent (Table 1).
Benzophenone has also been shown to mediate the
addition of aldehydes to other a,b-unsaturated ketones.
For example, Kraus reports that benzophenone-medi-
ated reaction of acetaldehyde with 2-cyclohexen-1-one
Table 2. Benzophenone-mediated reaction of 1,4-benzo-
quinone with benzaldehyde in SC-CO2
Solvent
Pressure (psi)
4672
Time (days)
Yield 3a (%)
SC-CO2+5%
t-BuOH
SC-CO2+5%
t-BuOH
3
2
2
49
44
44
Use of alcohols which possess abstractable a-hydrogens
as co-solvents (i.e. MeOH, EtOH, and i-PrOH) proved
unsuccessful, as high yields of the reduction product
(1,4-hydroquinone) were obtained at the expense of the
4548
SC-CO2
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R. Pacut et al. / Tetrahedron Letters 42 (2001) 1415–1418
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Table 3. Benzophenone-mediated reaction of 1,4-benzo-
Table 4. Benzophenone-mediated reaction of 2-cyclohexen-
1-one with acetaldehyde
quinone (1) with butyraldehyde in SC-CO2 and PhH
(time: 2 days)
Solvent
Pressure (psi)
Time (days)
Yield 6 (%)
Solvent
Pressure (psi)
Yield 3b (%)
PhH+5%
t-BuOH
SC-CO2+5%
t-BuOH
3
2
2
59
48
30
SC-CO2
SC-CO2
SC-CO2
SC-CO2
SC-CO2
SC-CO2
SC-CO2+5% t-BuOH
PhH+5% t-BuOH
1191
1492
1946
3042
5860
8180
5735
53
41
41
50
60
65
81
74
6320
5730
SC-CO2
placed in the reactor. The reactor was then sealed and
brought to 50°C. Following several argon purges to
remove oxygen, the reactor was pressurized with CO2
and allowed to equilibrate at 50°C and the desired
pressure for 30 minutes. (Note: During pressurization,
the glass ampoule ruptures.) A Pyrex® filter was placed
on the reactor, and the reaction mixture was irradiated
with a 150 W Xenon arc lamp for 2–3 days. Following
illumination, the contents of the reactor were bubbled
slowly into 12 mL of ethyl acetate cooled to 0°C. After
depressurization, the reactor was washed with ethyl
acetate and the combined washing analyzed by GC
(after addition of phenyl ether as an internal standard).
in PhH gives 3-acetylcyclohexanone (6) in 40% yield
(Scheme 4).3 Our results for this reaction are summa-
rized in Table 4. Under dilute conditions in PhH (t-
BuOH co-solvent), the yield improves to 59%. In
SC-CO2, the yield is nearly 50% with 5% t-BuOH
present, but drops to 30% in the absence of co-solvent
(presumably because of solubility issues).
The results described herein demonstrate that SC-CO2
is a viable replacement for benzene for the photo-
induced addition of aldehydes to a,b-unsaturated car-
bonyl compounds. The major obstacle to overcome is
related to the poor solubility of organic compounds in
the non-polar SC-CO2 solvent. However, this work
demonstrates that this problem is readily solved by
either (a) including an alcoholic co-solvent (specifically
t-BuOH) to increase solvent polarity, or (b) conducting
the reaction at higher CO2 pressures (where the solubi-
lizing power of SC-CO2 is enhanced).
Note: Because of the hazards associated with high
pressure work, we were especially careful to ensure that
the pressures utilized in this study did not exceed the
specifications of our system (ca. 15,000 psi).
Acknowledgements
Financial support from the US Environmental Protec-
tion Agency and National Science Foundation (CHE-
9524986) is acknowledged and appreciated.
One of the limitations of this chemistry is the long
reaction times, which reflect the fact that the reaction
products absorb light effectively. The Kraus group is
working on developing conditions that render the
product insoluble so as to shorten reaction times. Thus,
though the use of SC-CO2 solvent is an important step,
it is not the final step in making this reaction truly
benign.
References
1. Kraus, G. A.; Kirihara, M. J. Org. Chem. 1992, 57,
3256–3257.
2. Kraus, G. A.; Kirihara, M.; Wu, Y. In Benign by Design:
Alternative Synthetic Design for Pollution Prevention;
Anastas, P. T.; Farris, C. A., Eds.; ACS Symposium
Series 577; American Chemical Society: Washington,
D.C., 1994; pp. 76–83.
3. Kraus, G. A.; Liu, P. Tetrahedron Lett. 1994, 35, 7723–
7726.
4. McHugh, M.; Krukonis, V. Supercritical Fluid Extrac-
tion: Principles and Practice; Butterworths: Boston, 1986.
5. Eckert, C. A.; Knutson, B. L.; Debenedetti, P. G. Nature
1996, 383, 313–318.
General procedure for reactions in SC-CO2 solvent. The
reactor (17 mL capacity) and apparatus for performing
photochemistry in supercritical carbon dioxide was
described in earlier publications.10 In a typical proce-
dure, to a 2 mL glass ampoule was added 1.7 mmol of
aldehyde, 0.255 mmol of a,b-unsaturated ketone, and
0.255 mmol of benzophenone. In cases where a co-sol-
vent was used, 0.85 mL was added. The ampoule was
attached to a vacuum line, degassed three times by
freeze–pump–thaw method, sealed under vacuum and
6. Savage, P. E.; Gopalan, S.; Mizan, T. I.; Martino, C. J.;
Brock, E. E. AIChE J. 1995, 41, 1723–1778.
7. Chemical Synthesis Using Supercritical Fluids; Jessop, P.
G.; Leitner, W., Eds.; Wiley-VCH: Weinheim, 1999.
8. Johnston, K. P. In Supercritical Fluid Science and Tech-
nology; Johnston, K. P.; Penninger, J. M. L., Eds.; ACS
Symposium Series 406; American Chemical Society:
Washington, D.C., 1989; pp. 1–12.
Scheme 4.

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R. Pacut et al. / Tetrahedron Letters 42 (2001) 1415–1418
9. Hawthorne, S. B. Anal. Chem. 1990, 62, 633A–642A.
M. In Benign by Design: Alternative Synthetic Design for
Pollution Prevention; Anastas, P. T.; Farris, C. A., Eds.;
ACS Symposium Series 577; American Chemical Society:
Washington, D.C., 1994; pp. 98–113.
10. For details regarding the apparatus used for these experi-
ments, see: Tanko, J. M.; Blackert, J. F. Science 1994,
263, 203–205. Tanko, J. M.; Blackert, J. F.; Sadeghipour,
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