Laser flash photolysis measurements of the kinetics of ring opening of the 2,2-diphenylcyclobutylcarbinyl radical

Full text of DOI:10.1021/jo000095n

J . Org. Chem. 2000, 65, 4447-4449
4447
oxyl radicals, which is “instant” on the nanosecond time
scale.6,7 Barton’s PTOC esters8,9 are especially good
sources of acyloxyl radicals because they have a long
wavelength chromophore centered at about 360 nm and
are cleaved with high efficiency by 355 nm light from a
Nd:YAG laser.10,11 PTOC ester 5 was prepared from (2,2-
diphenylcyclobutyl)acetic acid by the mild 2,2′-dipyridyl
disulfide bis-N-oxide method.12 Because of the potential
utility of radicals such as 3 as reporter groups for LFP
kinetic studies, we explored various synthetic pathways
for synthesis of the carboxylic acid on a multigram scale.
Details of convenient preparative sequences are provided
in the Supporting Information.
La ser F la sh P h otolysis Mea su r em en ts of
th e Kin etics of Rin g Op en in g of th e
2,2-Dip h en ylcyclobu tylca r bin yl Ra d ica l
Seung-Yong Choi, J ohn H. Horner, and
Martin Newcomb*
Department of Chemistry, Wayne State University,
Detroit, Michigan 48202
men@chem.wayne.edu
Received J anuary 24, 2000
Ring opening of the cyclopropylcarbinyl radical (1a ) to
the homoallyl radical (2a ) is one of the more familiar
radical rearrangements. The addition of aryl groups at
C2 in the cyclopropyl ring, such as in 1b, results in
radicals that ring open exceedingly fast, with lifetimes
at ambient temperatures of only a few picoseconds.1,2
Such ultrafast radical rearrangements have been incor-
porated into mechanistic probes that can compete ef-
fectively against any follow-up reaction of a transient
radical intermediate. Phenyl-substituted cyclopropyl-
carbinyl radicals also are useful for mechanistic and
kinetic studies that employ laser flash photolysis (LFP)
methods because the benzylic and diphenylalkyl radical
products have chromophores in a relatively clean region
of the UV spectrum, at about 320 and 335 nm, re-
spectively.3-5
Photolysis of THF solutions containing PTOC ester 5
with 355 nm light from a Nd:YAG laser initially gave
acyloxyl radical 6 and the pyridine-2-thiyl radical (7),
which has λmax at 490 nm.13 Decarboxylation of 6 gave
radical 3 “instantly”, and the signal from radical 4
evolved with time. Figure 1 shows a time-resolved
spectrum obtained at -20 °C. The traces in the main
figure were “baseline adjusted” by subtraction of the
initially observed spectrum from subsequent spectra, and
the only apparent change on the short time scale em-
ployed is the growth of the signal at λmax ) 335 nm, which
is the expected region for absorbance from radical 4.14
The inset shows the initial spectrum obtained 30 ns after
firing the laser; the strong bleaching centered at about
360 nm is due to destruction of precursor 5, and the
absorbance at 490 nm is due to radical 7 that was formed
instantly.
The very fast fragmentations of radical 1b and other
aryl-substituted cyclopropylcarbinyl radicals are ap-
propriate for many studies, but they are too fast for one
type of mechanistic investigation. Specifically, if a radical
such as 1b were formed in a radical-radical or radical-
ion pair, ring opening would occur faster than diffusion-
limited processes that lead to diffusively free species. We
desired a relatively fast, UV-detectable radical probe
element that could “report” only on diffusively free
intermediates to complement the aryl-substituted cyclo-
propylcarbinyl probes. We describe here the calibration
of such a reaction, ring opening of the 2,2-diphenylcy-
clobutylcarbinyl radical (3) to radical 4.
The kinetics of formation of radical 4 were measured
in the temperature range -50 to 0 °C. Typical temper-
ature fluctuations during the course of a run were 0.1
°C at 0 °C and 0.6 °C at -50 °C. The random error
introduced by temperature fluctuations apparently was
the largest source of error. Complete kinetic results are
provided in the Supporting Information and are shown
graphically in Figure 2.
(4) Horner, J . H.; Tanaka, N.; Newcomb, M. J . Am. Chem. Soc. 1998,
120, 10379-10390.
(5) Furxhi, E.; Horner, J . H.; Newcomb, M. J . Org. Chem. 1999, 64,
4064-4068.
(6) Falvey, D. E.; Schuster, G. B. J . Am. Chem. Soc. 1986, 108,
7419-7420.
(7) Bockman, T. M.; Hubig, S. M.; Kochi, J . K. J . Org. Chem. 1997,
62, 2210-2221.
Resu lts a n d Discu ssion
(8) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron 1985,
41, 3901-3924.
(9) Crich, D.; Quintero, L. Chem. Rev. 1989, 89, 1413-1432.
(10) Bohne, C.; Boch, R.; Scaiano, J . C. J . Org. Chem. 1990, 55,
5414-5418.
For LFP kinetic studies, alkyl radicals are conveniently
produced by decarboxylation of the corresponding acyl-
(11) Ha, C.; Horner, J . H.; Newcomb, M.; Varick, T. R.; Arnold, B.
R.; Lusztyk, J . J . Org. Chem. 1993, 58, 1194-1198.
(12) Barton, D. H. R.; Chen, C.; Wall, G. M. Tetrahedron 1991, 47,
6127-6138.
(1) Newcomb, M.; J ohnson, C. C.; Manek, M. B.; Varick, T. R. J .
Am. Chem. Soc. 1992, 114, 10915-10921.
(2) Newcomb, M.; Choi, S. Y.; Toy, P. H. Can. J . Chem. 1999, 77,
1123-1135.
(13) Alam, M. M.; Watanabe, A.; Ito, O. J . Org. Chem. 1995, 60,
3440-3444.
(3) Newcomb, M.; Tanaka, N.; Bouvier, A.; Tronche, C.; Horner, J .
H.; Musa, O. M.; Martinez, F. N. J . Am. Chem. Soc. 1996, 118, 8505-
8506.
(14) Chatgilialoglu, C. In Handbook of Organic Photochemistry;
Scaiano, J . C., Ed.; CRC Press: Boca Raton, FL, 1989; Vol. 2, pp 3-11.
10.1021/jo000095n CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/13/2000

4448 J . Org. Chem., Vol. 65, No. 14, 2000
Notes
carbinyl19 radicals, one would have expected the differ-
ence in kinetics of ring openings of radicals 3 and 1b to
be 4 orders of magnitude. In fact, the difference in rate
constants for ring opening of the (trans-2-phenylcyclobu-
tyl)methyl22 radical (8) and the (trans-2-phenylcyclopro-
pyl)methyl1,18,19 radical (9) is almost exactly 4 orders of
magnitude. Thus, the ring opening of 3 is faster than
expected; this results from a considerable reduction in
the activation energy for cleavage of 3 relative to that
found for radical 8 (about 3 kcal/mol), which more than
offsets an entropic term for 3 that is slightly less
favorable than that of 8.22 High-level computations have
shown that the kinetics of ring openings of cyclopropyl-
carbinyl radicals are influenced by subtle steric effects
in the transition states,23,24 and we speculate that ring
opening of radical 3 might be accelerated by relief of
strain energy from an interaction involving the cis-phenyl
group.
F igu r e 1. Time-resolved spectra from reaction of radical 3
in THF at -20 °C. The spectra are from 60, 40, and 30 ns
with data from 20 ns subtracted to give a baseline. Symbols
on the 60 ns trace show the monitoring wavelengths. The inset
shows the actual spectrum observed at 20 ns.
Our objective in studying the ring opening of radical 3
was to obtain a well calibrated, radical reaction that
provided a strong chromophore in the product for use in
LFP applications and reacted less rapidly than diffu-
sional processes. In a mechanistic study, any rearrange-
ment of radical 3 or other 2-aryl-substituted cyclobutyl-
carbinyl radicals must occur from diffusionally free
species. This property complements that of the corre-
sponding diphenylcyclopropylcarbinyl radicals such as
1b, which fragment fast enough to compete with coupling
reactions within a radical-radical or radical-ion pair.
Rearrangement of radical 3 also provides two other
potentially useful facets. It can serve as a calibrated
radical clock, somewhat faster than the cyclopropylcarbi-
nyl radical, with rate constants determined at least as
precisely as those of the cyclopropylcarbinyl radical.19 In
addition, the high precision in the Arrhenius parameters
found in this work could prove useful for computational
chemists who wish to evaluate their methods for calcula-
tions of aryl-substituted radical systems, which are
notoriously difficult to handle computationally.
F igu r e 2. Kinetics of ring opening of radical 3 in THF. The
line is eq 1.
The rate constants for ring opening of radical 3 ranged
from 1.6 × 107 s-1 at -50 °C to 1.4 × 108 s-1 at 0 °C. In
the configuration of the kinetic spectrometer used for this
study, an instantaneous impulse signal gave a measured
rate of growth of 5 × 108 s-1. Convolution of this
instrument response with the fast rate constants mea-
sured at 0 °C is relatively unimportant. Data obtained
at temperatures greater than 0 °C were convoluted with
the instrument response and are not reported. Only data
acquired after the end of the laser pulse was used for
the kinetic solutions.
Exp er im en ta l Section
The Arrhenius function for ring opening of 3 is given
in eq 1
(2,2-Dip h en ylcyclobu tyl)a cetic Acid 2-Th ioxo-2H-p yr i-
d in -1-yl Ester (5). To a solution of (2,2-diphenylcyclobutyl)acetic
acid (see Supporting Information) (200 mg, 0.75 mmol) and 2,2′-
dipyridyl disulfide bis-N-oxide12 (208 mg, 0.83 mmol) in dry CH2-
log(k/s-1) ) (12.17 ( 0.09) - (5.04 ( 0.10)/θ (1)
where θ ) 2.3RT in kcal/mol and the listed errors are at
2σ. The precision in the Arrhenius parameters is note-
worthy in that it is better than the precision in the
determinations of the second-order rate constants for
reactions of radicals with hydrogen atom transfer trap-
ping agents that are used to calibrate radical clocks via
indirect studies.15-17 From eq 1, one calculates a rate
constant for ring opening of radical 3 of 2.54 × 108 s-1 at
20 °C. This reaction is about 3 orders of magnitude less
rapid at 20 °C than ring opening of the corresponding
cyclopropylcarbinyl system, the (2,2-diphenylcyclopropyl)-
methyl radical (1b).1,18,19
(15) Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J . C. J . Am. Chem.
Soc. 1981, 103, 7739-7742.
(16) J ohnston, L. J .; Lusztyk, J .; Wayner, D. D. M.; Abeywickreyma,
A. N.; Beckwith, A. L. J .; Scaiano, J . C.; Ingold, K. U. J . Am. Chem.
Soc. 1985, 107, 4594-4596.
(17) Franz, J . A.; Bushaw, B. A.; Alnajjar, M. S. J . Am. Chem. Soc.
1989, 111, 268-275.
(18) The rate constants for ring opening of aryl-substituted cyclo-
propylcarbinyl radicals given in ref 1 should be adjusted for the recent
recalibration of the rate constants for reactions of PhSeH with alkyl
radicals (ref 19). The rate constant for ring opening of the (2,2-
diphenylcyclopropyl)methyl radical at 20 °C is 4 × 1011 s-1, and that
for ring opening of the (trans-2-phenylcyclopropyl)methyl radical is 1.6
× 1011 s-1
.
(19) Newcomb, M.; Choi, S.-Y.; Horner, J . H. J . Org. Chem. 1999,
64, 1225-1231.
(20) Beckwith, A. L. J .; Moad, G. J . Chem. Soc., Perkin Trans. 2
1980, 1083-1092.
(21) Ingold, K. U.; Maillard, B.; Walton, J . C. J . Chem. Soc., Perkin
Trans. 2 1981, 970-974.
(22) Newcomb, M.; Horner, J . H.; Emanuel, C. J . J . Am. Chem. Soc.
1997, 119, 7147-7148.
(23) Martinez, F. N.; Schlegel, H. B.; Newcomb, M. J . Org. Chem.
1996, 61, 8547-8550.
On the basis of the kinetics of ring openings of
unsubstituted cyclobutylcarbinyl20,21 and cyclopropyl-
(24) Martinez, F. N.; Schlegel, H. B.; Newcomb, M. J . Org. Chem.
1998, 63, 3618-3623.

Notes
J . Org. Chem., Vol. 65, No. 14, 2000 4449
Cl2 (5 mL) in a 25 mL flask wrapped with aluminum foil and
placed in an ice-salt bath was added n-Bu3P (190 µL, 0.75 mmol)
under N2. The reaction mixture was stirred for 40 min at room
temperature and diluted with 10 mL of CH2Cl2. The solution
was washed with 10% Na2CO3, and the aqueous layer was
extracted with CH2Cl2. The combined organic extracts were
washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The crude product was isolated by column
chromatography on silica gel (1:1, hexanes/ethyl acetate) to yield
200 mg (0.53 mmol, 71%) of 5 as a yellow oil. The sample was
judged to be 90% pure on the basis of the NMR spectra. 1H
NMR: δ 1.98 (m, 1H), 2.26 (dd, J ) 16.8 Hz, J ) 6.4 Hz, 1H),
2.33-2.49 (m, 2H), 2.67 (dd, J ) 16.4 Hz, J ) 5.2 Hz, 1H), 3.05
(m, 1H), 3.78 (m, 1H), 6.58 (dt, J ) 6.8 Hz, J ) 2.0 Hz, 1H),
7.15-7.33 (m, 11H), 7.40 (dd, J ) 6.8 Hz, J ) 1.6 Hz, 1H), 7.64
(dd, J ) 7.8 Hz, J ) 1.6 Hz, 1H). 13C NMR: δ 23.5, 31.9, 35.4,
38.7, 53.8, 112.5, 125.8, 126.3, 126.4, 127.8, 128.3, 128.3, 133.5,
137.3, 137.5, 143.4, 149.8, 167.9, 175.7.
solutions were thermally equilibrated in a jacketed addition
funnel with continuous He sparging through a gas dispersion
tube. Temperature control was accomplished by circulating
solution from a temperature-regulated bath through the outer
jacket of the addition funnel. The solutions were allowed to flow
through a 1 cm × 1 cm quartz flow cell of conventional design
at a rate of ca. 20 mL/min; under the conditions used, a fresh
solution of precursor was used for each pulse experiment. The
reaction temperatures were measured with a thermocouple
inserted in the flowing stream a few millimeters above the
irradiation zone. Detailed results are given in Supporting
Information. Typical errors in the kinetic solutions were <5%.
Ack n ow led gm en t. This work was supported by
grants from the National Science Foundation (CHE-
9614968 and CHE-9981746).
Su p p or tin g In for m a tion Ava ila ble: Experimental meth-
ods for preparation of (2,2-diphenylcyclobutyl)acetic acid, NMR
spectra of new compounds, and kinetic results for ring opening
reactions of radical 3. This material is available free of charge
via the Internet at http://pubs.acs.org.
Kin etic stu d ies were accomplished with an Applied Photo-
physics LK-50 kinetic spectrometer employing a Nd:YAG laser
for production of 355 nm light (ca. 40 mJ /pulse). Data were
acquired with a 2 GHz digitization rate. Dilute solutions of
radical precursor
5 in THF were prepared such that the
absorbance at 355 nm was 0.4-0.5 (ca. 3 × 10-5 M). The
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