Absolute rate constants for water protonation of 1-(3-benzoylphenyl)alkyl carbanions.

Article abstract of DOI:10.1021/ol0263752

[reaction: see text] Efficient photodecarboxylation of (3-benzoylphenyl)alkanoic acids with formation of carbanions has enabled the determination of their protonation rate constants in water; the values obtained show that the reactivity toward protonation

Full text of DOI:10.1021/ol0263752

ORGANIC
LETTERS
2002
Vol. 4, No. 18
3083-3085
Absolute Rate Constants for Water
Protonation of 1-(3-Benzoylphenyl)alkyl
Carbanions
,†
,‡
Gonzalo Cosa,† Laura Llauger,† J. C. Scaiano,* and Miguel A. Miranda*
Department of Chemistry, UniVersity of Ottawa, 10 Marie-Curie,
Ottawa, Ontario K1N 6N5, Canada, and Departamento de Qu´ımica/Instituto de
Tecnolog´ıa Qu´ımica UPV-CSIC, UniVersidad Polite´cnica de Valencia,
AVenida de los Naranjos s/n, 46022-Valencia, Spain
tito@photo.chem.uottawa.ca
Received June 17, 2002
ABSTRACT
Efficient photodecarboxylation of (3-benzoylphenyl)alkanoic acids with formation of carbanions has enabled the determination of their protonation
rate constants in water; the values obtained show that the reactivity toward protonation is determined by the size of the alkyl groups attached
to the carbanion center.
A nonsteroidal antiinflammatory drug commercially known
as ketoprofen presents unusual pH-dependent photo-
chemistry.1-6 In particular, the acid form of ketoprofen
behaves as a conventional benzophenone, with high inter-
system crossing yields and triplet radical-like behavior.4,5 In
contrast, the carboxylate form undergoes efficient photo-
decarboxylation within the duration of a nanosecond laser
pulse to yield a carbanion,4,7,8 which is responsible for the
formation of 3-ethylbenzophenone.9
This prompt photochemical source of carbanions provides
the key to generating very interesting reactive intermediates
for mechanistic studies. Thus, beyond their importance as
intermediates involved in the photodegradation of a phar-
maceutical product, they provide an attractive tool in order
to explore the chemistry of carbanions in different systems,
in particular, water.
† University of Ottawa.
‡ Universidad Polite´cnica de Valencia.
(1) Bosca´, F.; Miranda, M. A.; Carganico, G.; Mauleo´n, D. Photochem.
Photobiol. 1994, 60, 96-101.
We have thus directed our efforts toward gaining an insight
into carbanion reactivity. To that effect we synthesized
compounds 3 and 4, which in combination with the com-
(2) Chignell, C. F.; Sik, R. H. Photochem. Photobiol. 1995, 62, 205-
207.
(3) de la Pen˜a, D.; Mart´ı, C.; Nonell, S.; Mart´ınez, L. A.; Miranda, M.
A. Photochem. Photobiol. 1997, 65, 828-832.
(4) Mart´ınez, L. J.; Scaiano, J. C. J. Am. Chem. Soc. 1997, 119, 11066-
11070.
(5) Monti, S.; Sortino, S.; De Guidi, G.; Marconi, G. J. Chem. Soc.,
Faraday Trans. 1997, 93, 2269-2275.
(6) Monti, S.; Sortino, S.; De Guidi, G.; Marconi, G. New. J. Chem.
1998, 22, 599-604.
(7) Cosa, G.; Mart´ınez, L. J.; Scaiano, J. C. Phys. Chem. Chem. Phys.
1999, 1, 3533-3537.
(8) Borsarelli, C. D.; Braslavsky, S. E.; Sortino, S.; Marconi, G.; Monti,
S. Photochem. Photobiol. 2000, 72, 163-171.
(9) Constanzo, L. L.; De Guidi, G.; Condorelli, G.; Cambria, A.; Fama,
M. Photochem. Photobiol. 1989, 50, 359-365.
10.1021/ol0263752 CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/31/2002

mercially available analogues 1 and 2 render a complete set
of precursors for the generation of primary, secondary, and
tertiary 1-(3-benzoylphenyl)alkyl carbanions. These inter-
mediates have been submitted to kinetic and spectroscopic
investigation, following light-induced photodecarboxylation
of 1-4.
Figure 2. These traces follow first-order kinetics and lead to
the rate constants presented in Table 1.
Laser excitation (308 nm) of compounds 1, 3, and 4 in
0.1 M KOH aqueous solutions gives rise to transient
absorption spectra similar to those observed following laser
flash photolysis of ketoprofen (compound 2).4,5,7 These
spectra, including that of the ketoprofen carbanion, are shown
in Figure 1. Note that they have been normalized in the
visible region.
Figure 2. Normalized decay traces (λ ) 600 nm) for the transients
obtained following 308 nm laser excitation of 1-4 in a 0.1 M KOH
aqueous solution (a few points are shown to assist in the visualiza-
tion). (b) Starting from 1; (0) starting from 2; (2) starting from 3;
(O) starting from 4. Solutions were equilibrated under N2O.
An analysis of Figure 2 and of the data of Table 1 shows
a large effect attributable to alkyl substitution on the decay
rate constant of the carbanions. Introduction of a first methyl
group in structure 1 increases the lifetime of the resulting
secondary carbanion by a factor of 5.
Figure 1. Normalized transient absorption spectra obtained fol-
lowing 308 nm laser excitation of 1-4 in a KOH 0.1 M, 1% v/v
MeOH aqueous solution. From front to back: from 1, 16 ns after
the laser pulse; from 2, 48 ns after the laser pulse; from 3, 48 ns
after the laser pulse; from 4, 64 ns after the laser pulse. Solutions
were equilibrated under N2O. Experimental points were acquired
at 10 nm intervals.
Inclusion of a second alkyl group (structures 3 and 4)
increases the lifetime of the resulting tertiary carbanion by
a factor of ca. 10 with respect to the primary carbanion (1).
The change is not so marked with respect to the secondary
carbanion (the lifetime is only twice as long). There is also
a slight difference in the lifetime of the carbanions photo-
generated from 3 and 4, the latter being longer lived.
Product studies performed with 1 and other ketoprofen
derivatives have demonstrated that the photodecarboxylation
pattern characteristic of ketoprofen is in fact a common
denominator in (aroylphenyl)alkyl carboxylic acids.10 Our
results obtained with a series of 2-(3-benzoylphenyl)alkyl
carboxylic acids further confirm these results. Thus, the
transient absorption spectra obtained are independent of the
acid employed and in all cases are equal to that of the
ketoprofen carbanion. Further, product studies (see also Table
1) reveal that for compounds 3 and 4, photodecarboxylation
and protonation of the corresponding carbanions occur with
quantum yields similar to that of ketoprofen.
The visible part of the spectrum is common to all species,
with a broad maximum located at ca. 580 nm (see also Table
1). In the case of the carbanion from 1, a shoulder is
Table 1. Quantum Yields of Photodecarboxylation of
(3-Benzoylphenyl)alkanoic Acids and Absorption Maxima and
Protonation Rate Constants for the Photogenerated carbanions
a
compd
Φphotodec
λ max/nm
kH+/s-1
1
2
3
4
0.66b
0.75c
0.76
570
570
580
580
26.8 ( 0.3 × 106
4.63 ( 0.04 × 106
2.17 ( 0.05 × 106
2.04 ( 0.05 × 106
0.73
In the series studied, all the carbanions generated upon
photoexcitation can only decay via protonation by water
(considering that KOH 0.1 M was employed in these
experiments, protonation by free H+ can be ruled out). Thus,
the trends in decay rate constants presented in Table 1 are
interesting;11,12 they show that a primary carbanion reacts
a Values are means of three independent measurements. b From ref 10.
c From ref 9.
noticeable at ca. 520 nm. This is due to a contribution by
absorption from the triplet state of 1, as determined from
time windows monitored at longer times following excitation
(data not shown). This is similar to the situation found for
ketoprofen following irradiation in basic acetonitrile/water
mixtures with xwater ) 0.13.7
(10) Xu, M.; Wan, P. Chem. Commun. 2000, 2147-2148.
(11) March, J. AdVanced Organic Chemistry; 4th ed.; Wiley & Sons:
New York, 1992.
(12) Interestingly, these rate constants are much lower than those recently
reported for protonation at oxygen in transient enolates: Richard, J. P.;
Williams, W.; O’Donoghue, A. M. C.; Amyes, T. L. J. Am. Chem. Soc.
2002, 124, 2957-2968.
The time evolution of the transient absorption for the
carbanions from 1 to 4, recorded at 600 nm, is shown in
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Org. Lett., Vol. 4, No. 18, 2002

faster than a secondary one, which in turn is more reactive
than a tertiary carbanion. Lower carbanion stabilization is
an unlikely explanation for the observed tendency. Such
lower stabilization should be accompanied by a bathochromic
shift of the carbanion spectra; no such shift is observed when
comparing carbanions from 3 or 4 with that from 1. Further,
the carbanion stability order is tertiary < secondary <
primary < methyl, given that substitution by electron-
donating alkyl groups results in a greater negative charge
density at the carbanion central carbon atom.11 Thus, the
trend in protonation is contrary to expectations based on
charge stabilization.
Instead, a more satisfactory explanation is that protonation
is determined by entropic rather than enthalpic factors. In
fact, resonance with the benzoylphenyl group, common to
all these carbanions, would account for most of the stabiliza-
tion effects. This makes negligible the role of alkyl substitu-
tion, thus resulting in all these carbanions showing only
minor enthalpic differences. Conversely, the reactivity is
clearly determined by the size of the alkyl groups attached
to the carbanion center, and steric hindrance to protonation
appears to control the reactivity with bulkier groups. This
would also account for the slight difference observed in the
protonation rates of carbanions photogenerated from 3 and
4, where the cyclopentyl ring existing in the tertiary
carbanion generated from 4 would add an extra constraint
compared to the tertiary carbanion from 3.
While steric effects on solvolysis are not unexpected,
absolute rate constants for these processes are generally
unavailable. Our studies have shown the possibility of
obtaining absolute rate constants for the reactions of car-
banions in water. Our results support the data published by
Dorfman and co-workers,13 which to our knowledge are the
only reported absolute reactivities of simple benzylic car-
banions.
Acknowledgment. J.C.S. thanks NSERC (Canada) for
generous financial support. G.C. thanks the Ontario Graduate
Scholarship Program for a postgraduate scholarship.
Supporting Information Available: Experimental pro-
1
cedure for compounds 3 and 4 and their HRMS, H NMR,
and 13C NMR characterization, as well as that for their
precursors and photoproducts. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL0263752
(13) Bockrath, B.; Dorfman, L. M. J. Am. Chem. Soc. 1974, 96, 5708-
5715, Bockrath, B.; Dorfman, L. M. J. Am. Chem. Soc. 1975, 97, 3307-
3310.
Org. Lett., Vol. 4, No. 18, 2002
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