Intermolecular photodecarboxylation of electron-deficient substrates by phthalimides in water: Efficiency, selectivity and online monitoring

Article abstract of DOI:10.1039/c2gc36089f

The intermolecular photodecarboxylation of arylacetic acids 3-5 in water by use of stoichiometric amounts of N-alkylated phthalimides 1a,b was investigated by NMR and online pH- and CO₂-release sensing. Decreasing the electron donor capability of the arylacetic acids by 4-fluoro and trifluoromethyl substitution alters the efficiency of the photodecarboxylation and selectivity of the secondary reaction. A remarkable switch in reaction channel (A to B) was observed for perfluoropropionic acid.

Full text of DOI:10.1039/c2gc36089f

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Intermolecular photodecarboxylation of electron-deficient substrates by
phthalimides in water: efficiency, selectivity and online monitoring†
Axel G. Griesbeck,* Nestor Nazarov, Jörg M. Neudörfl and Maria Heffen
Received 13th July 2012, Accepted 30th August 2012
DOI: 10.1039/c2gc36089f
The intermolecular photodecarboxylation of arylacetic acids
3–5 in water by use of stoichiometric amounts of N-alkylated
phthalimides 1a,b was investigated by NMR and online pH-
and CO2-release sensing. Decreasing the electron donor
capability of the arylacetic acids by 4-fluoro and trifluoro-
methyl substitution alters the efficiency of the photo-
decarboxylation and selectivity of the secondary reaction.
A remarkable switch in reaction channel (A to B) was
observed for perfluoropropionic acid.
Intramolecular photodecarboxylation of phthaloyl ω-amino car-
boxylic acids in aqueous media is a powerful route to medium-
Scheme 1 Photoinduced phthalimide-initiated decarboxylation and
sized and large ring systems1 and was, among many other
subsequent competing addition/reduction channels A and B.
applications,2–4 used in the last decade for the synthesis of cyclo-
peptides5 and cycloalkynes.6 This process can be conducted in
water in the presence of acetone as a co-solvent with triplet-
sensitizing properties.7 Mechanistically, this process involves the
triplet state of the phthalimide which acts as the oxidant in an
intramolecular photoinduced electron transfer (PET).8 Oxidation
of the carboxylate group and rapid CO2 release results in a
carbon-centered radical that combines with the phthalimide
radical anion. The intermolecular version of this process is an
efficient method for the generation of carbon-centered radicals in
water.9 These radicals combine with the phthalimide radical
Scheme 2 Phthalimide substrates and carboxylates.
anion (channel A) which corresponds to a Grignard-like
addition10 or are reduced via back electron transfer with for-
stoichiometric amounts in order to detect the product compo-
mation of the corresponding carbanions that are subsequently
sition after full conversion of the carboxylates (Scheme 2).
In order to analyse the kinetic and the chemoselectivity of the
protonated (channel B) to give the alkanes RH (Scheme 1).
The efficiencies of the two subsequent electron-transfer pro-
process, several parameters were detected using sampling
cesses, PET and reduction of the carbon-centered radicals, are
(NMR) or online (CO2 formation and pH change) detection.11
obviously dependent on the redox potentials of the carboxylate
and the C-centered radical which are directly opposed. This
interconnection is investigated in this report by use of a systema-
tic series of arylacetates 3–5 and C2F5COOH (9, as a model
The literature-known benzylation of 1a was used as the standard
process (1a + 3).7 This reaction is of synthetic use for the prep-
aration of aristolactam precursors12 and has also been performed
under microreactor conditions.13 Under reaction conditions
compound for polyfluorinated tensides) and two N-alkylated
where the photolysis chamber is constantly purged with argon, a
continuous increase in pH was determined until complete con-
phthalimides, the N-methyl and N-isobutyl derivatives 1a and
1b, respectively. The phenylacetates 3–5 were applied as 10−3
M
version.9 This is due to the formation of hydroxyl anions from
protonation of the initially formed alkoxides 2 (Scheme 1) which
were also detected by time-resolved conductometry.14 When the
reaction progress was followed by online gas analysis in a closed
system, the pH change behaves analogously (Fig. 1). Compari-
son of the NMR traces with online pH profiles under open and
closed system conditions and with the CO2 release curve reveals
perfectly superimposable kinetic traces. For the standard
aqueous solutions with acetone as a cosolvent. In one series of
experiments, the phthalimides 1a and 1b were applied in
Department of Chemistry, Greinstr. 4, D-50939 Köln, Germany.
E-mail: griesbeck@uni-koeln.de; Fax: +0049-221-4705057
†CCDC 876009 (7a) and 876010 (8a). For crystallographic data in CIF
or other electronic format see DOI: 10.1039/c2gc36089f
3004 | Green Chem., 2012, 14, 3004–3006
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Fig. 3 Online pH and CO2 release traces of the photochemical reaction
of phthalimide 1a and 4-(trifluoromethyl)phenylacetate (5) in aqueous
solution at room temperature, λexc = 300 nm: 95% conversion after
14.5 h.
Fig. 1 Online pH and CO2 release traces of the photochemical reaction
of phthalimide 1a and phenylacetate (3) in aqueous solution at room
temperature, λexc = 300 nm: 95% conversion after 2.5 h.
Scheme 3 Phthalimide decarboxylation/addition photochemistry.
Fig. 2 Online pH and CO2 release traces of the photochemical reaction
of phthalimide 1a and 4-fluorophenylacetate (4) in aqueous solution at
room temperature, λexc = 300 nm: 95% conversion after 8 h.
Fig. 4 Structures of 7a and 8a in the crystal.
which X-ray structure analyses could be performed for 7a and
8a (Fig. 4).‡
reaction, leading to 6a, 95% conversion was detected after 2 h
by NMR and after 150 min by CO2 determination. There is no
trace of side-products in the NMR spectra and the chemical yield
by extraction work-up and recrystallization was 81%
(Scheme 3).
The complete conversion of both carboxylate and phthalimide
substrates was determined by NMR spectroscopy of the crude
reaction mixture, indicating that the formation of the addition
products is the exclusive pathway (channel A in Scheme 1) for
all arylacetic acid combinations with compound 1a.
From time-resolved conductivity measurements and laser-
flash experiments, the quantum yield for product (6a) formation
from the donor–acceptor–donor pair 1a/3 was determined as 0.2
at neutral pH.7 Assuming fast and irreversible CO2 formation fol-
lowing the primary PET, quantum yields for product formation
were determined for 7a15 as 0.07 and for 8a as 0.03 from the
initial slopes of the CO2-release kinetics (Fig. 1–3). The products
were easily isolated from the aqueous reaction mixture by salting
out and extraction with ethyl acetate. Recrystallization from
aqueous acetone resulted in the crystalline products 6–8 from
The N-isobutyl acceptor 1b showed the same trends in relative
reactivities and also resulted in similar yields of photoaddition pro-
ducts, however, additionally 4-fluorotoluene and 4-trifluorotoluene
were detected from the photolysis in the presence of 4 and 5,
respectively. Thus, the reduction of the intermediary benzylic
radical can compete with addition to the phthalimide radical
anion in this limiting case. In order to drive this process in
direction to the catalytic channel B, we investigated a highly
electron-deficient carboxylate, perfluoropropionic acid (9). This
compound serves as a model for the environmentally critical
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of channel B decay leading to perfluoroalkanes that could not be
detected in the reaction mixture. Thus, this process might consti-
tute a new tool for the photodegradation of PFT in aqueous
media without toxic reagents.
Notes and references
‡Crystal data for the 4-fluorophenyl-substituted compound 7a:
C16H14FNO2, colourless needles from aqueous acetone, M = 271.29, a =
9.5984(4), b = 9.3398(7), c = 14.7806(12), α, γ = 90°, β = 100.934(4)°,
monoclinic, space group P21/c, Mo-Kα, 2218 reflections with I > 2σ(I),
R = 0.0406, wR2 = 0.0673. Crystal data for the 4-trifluoromethylphenyl-
substituted compound 8a: C17H14F3NO2, colourless needles from
aqueous acetone, M = 321.29, a = 15.6286(10), b = 8.6250(7), c =
10.8601(5), α, γ = 90°, β = 96.661(4)°, monoclinic, space group P21/c,
Mo-Kα, 1896 reflections with I > 2σ(I), R = 0.0407, wR2 = 0.0723.
Crystallographic data for these structures have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publications
no. CCDC-876009 (7a) and CCDC-876010 (8a).
Fig. 5 Online pH and CO2 release traces of the photochemical reaction
of phthalimide 1b and perfluoropropionic acid (9) in aqueous solution at
room temperature, λexc = 300 nm: 95% conversion after 22 h.
Table 1 Photolysis of carboxylates 3–5 and 9 in the presence of
phthalimides 1a and 1ba
1 A. G. Griesbeck, A. Henz, K. Peters, E.-M. Peters and H. G. von Schner-
ing, Angew. Chem., Int. Ed., 1995, 34, 474–476.
1a
1b
2 A. G. Griesbeck, W. Kramer, T. Heinrich and J. Lex, Photochem. Photo-
biol. Sci., 2002, 1, 237–239.
Channel A
/B
Channel A
/B
3 A. G. Griesbeck, T. Heinrich, M. Oelgemöller, A. Heidtmann and
A. Molis, Helv. Chim. Acta, 2002, 85, 4561–4578.
4 M. Horvat, K. Mlinaric-Majerski, A. G. Griesbeck and N. Basaric,
Photochem. Photobiol. Sci., 2011, 10, 610–617.
5 A. G. Griesbeck, T. Heinrich, M. Oelgemöller, A. Molis and J. Lex,
J. Am. Chem. Soc., 2002, 124, 10972–10973.
3
4
5
9
81% 6ab
61% 7ab
70% 8ab
n.d.d
—
—
—
n.d.d
70% 6bb
60% 7bb
70% 8bb
27% 10b
—
10%c
15%c
73%c
6 D. J. Yoo, E. Y. Kim, M. Oelgemöller and S. C. Shim, Photochem.
Photobiol. Sci., 2004, 3, 311–316.
7 K.-D. Warzecha, H. Görner and A. G. Griesbeck, J. Phys. Chem. A,
2006, 110, 3356–3363.
a In a water–acetone (1 : 3) mixture, under N2, 15 °C, 300 nm, 0.1 M
concentration of 1 and carboxylic acid. b Isolated yield. c By 1H NMR
analysis of the crude reaction mixture. d Not determined.
8 A. G. Griesbeck, N. Hoffmann and K.-D. Warzecha, Acc. Chem. Res.,
2007, 40, 128–140.
9 A. G. Griesbeck, W. Kramer and M. Oelgemöller, Green Chem., 1999, 1,
205–207.
10 K. Heidenbluth, H. Toenjes and R. Scheffler, J. Prakt. Chem., 1965, 30,
204–217.
11 For infrared CO2 detection and pH control passport sensors were used
(PS-2110 for CO2 and CI-6507 A for pH) from PASCO company.
12 A. G. Griesbeck, K.-D. Warzecha, J. M. Neudörfl and H. Görner, Synlett,
2004, 2347–2350.
13 (a) V. Belluau, P. Noeureuil, E. Ratzke, A. Skvortsov, S. Gallagher,
C. A. Motti and M. Oelgemöller, Tetrahedron Lett., 2010, 51, 4738–
4741; (b) O. Shvydkiv, K. Nolan and M. Oelgemöller, Beilstein J. Org.
Chem., 2011, 7, 1055–1063; (c) O. Shvydkiv, S. Gallagher, K. Nolan and
M. Oelgemöller, Org. Lett., 2010, 12, 5170–5173.
14 H. Görner, M. Oelgemöller and A. G. Griesbeck, J. Phys. Chem. A,
2002, 106, 1458–1467.
15 F. Hatoum, S. Gallagher, L. Baragwanath, J. Lex and M. Oelgemöller,
Tetrahedron Lett., 2009, 50, 6335–6338.
16 A. B. Lindstrom, M. J. Strynar and E. L. Libelo, Environ. Sci. Technol.,
2011, 45, 7954–7961.
17 A. G. Griesbeck, A. Rehorek, N. Schlörer, J. Ohrem and N. Nazarov,
manuscript in preparation.
perfluorotensides (PFT, e.g. PFOA, Scheme 2) that are in the
focus of numerous studies concerning decomposition techniques
in wastewater treatment.16 Current photochemical decomposition
technologies rely mostly on vacuum UV irradiation, e.g. at
172 nm,17 or UV irradiation in the presence of strong inorganic
oxidants.18 The use of simple organic dyes such as the phthal-
imides as photocatalysts would facilitate the degradation of PFT.
The photolysis of 1b in the presence of 9 shows a similar CO2
release time profile as with the trifluoro compound 5 (Fig. 5). In
this case, a constant pH decrease was observed over the photo-
lyses time after a short induction period. Only one new product
was obtained in 27% relative yield: the addition product 10 of
the pentafluoroethyl fragment to the phthalimide 1b (Table 1).
This is the first example of a perfluoroalkylation in the context
of phthalimide photochemistry (Scheme 4). Furthermore, no
perfluoropropionic acid 9 was detected in the reaction mixture,
i.e. complete decomposition of 9 was achieved with about 73%
18 e.g. R. Dillert, D. Bahnemann and H. Hidaka, Chemosphere, 2007, 67,
785–792.
3006 | Green Chem., 2012, 14, 3004–3006
This journal is © The Royal Society of Chemistry 2012