Photoactivation of amino-substituted 1,4-benzoquinones for release of carboxylate and phenolate leaving groups using visible light

Article abstract of DOI:10.1021/jo060790g

Upon exposure to visible light, 2-pyrrolidino-substituted 3,6-dimethyl-1,4-benzoquinones photocyclize to give benzoxazolines with quantum yields of 0.07-0.10 in CH₂Cl₂, 0.02-0.04 in CH ₃CN, and <0.01 in 30% aq CH₃

Full text of DOI:10.1021/jo060790g

Photoactivation of Amino-Substituted 1,4-Benzoquinones for Release
of Carboxylate and Phenolate Leaving Groups Using Visible Light
Yugang Chen and Mark G. Steinmetz*
Department of Chemistry, Marquette UniVersity, Milwaukee, Wisconsin 53201-1881
mark.steinmetz@marquette.edu
ReceiVed April 13, 2006
Upon exposure to visible light, 2-pyrrolidino-substituted 3,6-dimethyl-1,4-benzoquinones photocyclize
to give benzoxazolines with quantum yields of 0.07-0.10 in CH2Cl2, 0.02-0.04 in CH3CN, and <0.01
in 30% aq CH3CN. With carboxylate or phenolate leaving groups incorporated via coupling to a
5-hydroxymethyl group of the quinones, the photocyclizations give benzoxazolines that eliminate the
leaving groups in a dark reaction. Lifetimes for elimination of 4-YC6H4OH in 30% phosphate buffer in
CD3CN (pD 7) at 17 °C are 13.1, 0.54, and 0.13 h for Y ) H, CF3, and CN, respectively, and the linear
equation log k (h-1) ) 0.998(-pKa) + 8.80 gives a best fit to the data. Carboxylate leaving groups are
rapidly eliminated upon photolysis of the quinones in aq CH3CN to produce an o-quinone methide
intermediate that is trapped by 4 + 2 cycloaddition with unreacted starting material or with added
3-(dimethylamino)-5,5-dimethyl-2-cyclohexen-1-one. The ortho-quinone methide is observed at 339 and
455 nm by conventional absorption spectroscopy and gives a pseudo-first-order fit of the decay kinetics
with τ1/2 ) 34.9 min in 30% phosphate buffer in CH3CN at 20 °C.
Introduction
to an unstable benzoxazoline photoproduct 4 that would expel
leaving groups (LG-) such as carboxylate groups or phenolate
groups in a subsequent dark elimination reaction. The 2-pyr-
rolidino-1,4-benzoquinone 3 could then serve as a photocleav-
able group that would unmask functionality upon activation
through the use of visible light. The use of visible light would
be important in differentiating among multiple photolabile
groups in the selective deprotection of polyfunctional mol-
ecules.4 Achieving such wavelength-selective photochemistry
can be considered one of the major challenges in photodepro-
tection chemistry. Among the potential difficulties is the fact
that few photocleavable groups are available that are sensitive
to light in the visible wavelength region. With few exceptions,5,6
Dialkylamino-substituted 1,4-benzoquinones have been shown
to undergo rearrangement to isomeric benzoxazolines when
exposed to sunlight.1 The photorearrangement has been exem-
plified by 2-pyrrolidino-1,4-benzoquinone 1, which gives ben-
zoxazoline 2 as a photoproduct (eq 1).2 In a previous commu-
nication,3 we considered the possibility that the structurally
related 2-pyrrolidino-1,4-benzoquinone 3 would photorearrange
(3) Part of this work has been published in preliminary form: Chen, Y.;
Steinmetz, M. G. Org. Lett. 2005, 7, 3729-3732.
(4) (a) Bochet, C. G. Tetrahedron Lett. 2000, 41, 6341-6346. (b) Bochet,
C. G. Angew. Chem., Int. Ed. 2001, 40, 2071-2073.
(1) (a) Cameron, D. W.; Giles, R. G. F. Chem. Commun. 1965, 573-
574. (b) Cameron, D. W.; Giles, R. G. F. J. Chem. Soc. C 1968, 1461-
1464. (c) Giles, R. G. F.; Mitchell, P. R. K.; Roos, G. H. P.; Baxter, I. J.
Chem. Soc., Perkin Trans. 1 1973, 493-496.
(2) Falci, K. J.; Franck, R. W.; Smith, G. P. J. Org. Chem. 1977, 42,
3317-3319.
(5) Furuta, T.; Wang, S. S.-H.; Dantzker, J. L.; Dore, T. M.; Bybee, W.
J.; Callaway, E. M.; Denk, W.; Tsien, R. Y. Proc. Natl. Acad. Sci. U.S.A.
1999, 96, 1193-1200.
(6) Banerjee, A.; Grewer, C.; Ramakrishnan, L.; Jager, J.; Gameiro, A.;
Breitinger, H.-G. A.; Gee, K. R.; Carpenter, B. K.; Hess, G. P. J. Org.
Chem. 2003, 68, 8361-8367.
10.1021/jo060790g CCC: $33.50 © 2006 American Chemical Society
Published on Web 07/04/2006
J. Org. Chem. 2006, 71, 6053-6060
6053

Chen and Steinmetz
SCHEME 1
SCHEME 2
the wavelengths that can be used for the photoremoval of
protecting groups lies below about 400 nm.
In this paper, we report in full on the photochemistry of
2-pyrrolidino-1,4-benzoquinones 3 which bear various carboxy-
late and para-substituted phenolate leaving groups, LG- (Scheme
1). Under aqueous conditions, the carboxylate leaving groups
are rapidly expelled upon photocyclization to the benzoxazolines
4. The loss of the carboxylate leaving groups produces a
trappable o-quinone methide intermediate, which can also be
observed by absorption spectroscopy. With the phenolate leaving
group the photocyclized product, 4, is observable by NMR
spectroscopy during photolyses under aqueous conditions, and
para-substituted phenolate derivatives of 4 can be isolated after
photolyses in nonaqueous solvents. Kinetics investigations of
the release of para-substituted phenolate groups give a linear
Bronsted-type correlation of release rates and leaving group
basicity from which the release times of the labile carboxylate
leaving groups from 4 can be estimated to be on the millisecond
time scale.
obtain 3 (LG- ) 4-YC6H4O-, Y ) CF3, CN) in 33% and 37%
yields, respectively (eq 2). This procedure circumvented the low
yields obtained from our previously reported route, which was
used to synthesize 3 (LG- ) PhO-).3
Results
Synthesis. 5-Hydroxymethyl-1,4-benzoquinone 6 was a key
intermediate in the synthesis of 2-pyrrolidino-1,4-benzoquinones
3 bearing carboxylate and para-substituted phenolate leaving
groups. The synthesis of 6 involved ortho formylation7 of 2,5-
dimethyl-4-methoxyphenol 78 to give the 2-hydroxybenzalde-
hyde 8 (Scheme 2), followed by sodium borohydride reduction9
of the aldehyde group, which furnished benzylic alcohol 9. The
phenolic ether 9 was oxidized10 to the quinone 10, which was
converted to 6 by reaction with pyrrolidine in the presence of
air to oxidize a hydroquinone intermediate that would be
expected to be formed in this reaction. The carboxylate leaving
groups (LG- ) PhCO2-, PhCH2CO2-, 4-CNC6H4CO2-) were
introduced by acylation of 6 using the corresponding acid
chlorides (Scheme 2). The 2-pyrrolidino-1,4-benzoquinones 3
were obtained as red-purple crystalline compounds that showed
strong absorption in the 450-650 nm wavelength region in
aqueous solution. Compounds 3 were stable in aqueous CD3-
CN in the dark and showed no signs of reaction for periods of
at least a week. Neat 6 was stable to storage for months at -22
°C.
Photolyses of Carboxylate Derivatives of 3. The photo-
chemistry of 2-pyrrolidino-1,4-benzoquinones 3 was initially
investigated with the benzoate derivative (LG- ) PhCO2-).
Photolysis of 0.02 M solutions in 30% D2O in 70% CD3CN
with a 120 W sunlamp produced benzoic acid in 58% yield at
100% conversion, according to 1H NMR spectroscopy. An
additional photoproduct, present in 36% yield, was chromato-
graphically isolated and identified by 1H and 13C NMR
spectroscopy and elemental analysis as 11 (eq 3). Compound
A Mitsunobu coupling procedure11 was used to introduce
phenolic groups at the hydroxymethyl group of quinone 6 to
(7) Hofslokken, N. U.; Skattebol, L. Acta Chem. Scand. 1999, 53, 258-
262.
(8) Godfrey, I. M.; Sargent, M. V. J. Chem. Soc., Perkin Trans. 1 1974,
1353-1354.
11 appeared to be a 1:1 mixture of diastereomers. Its structure
suggested that it could have been produced via cycloaddition
of the o-quinone methide intermediate 5 with starting material
3 (LG- ) PhCO2-). Consumption of 3 (LG- ) PhCO2-) by
such a cycloaddition during photolysis would account for the
less than 100% yield of released benzoic acid observed. Similar
(9) Witiak, D. T.; Loper, J. T.; Almerico, S. A. M.; Verhoef, V. L.; Filppi,
J. A. J. Med. Chem. 1989, 32, 1636-1642.
(10) Ott, R.; Pinter, E. Monatsh. Chem. 1997, 128, 901-909.
(11) (a) Mitsunobu, O. Synthesis 1981, 1-28. (b) Manhas, M. S.;
Hoffman, W. H.; Lal, B.; Bose, A. K. J. Chem. Soc., Perkin Trans. 1 1975,
461-463. (c) McCarthy, J. R.; Wiedeman, P. E.; Schuster, A. J.; Whitten,
J. P.; Barbuch, R. J.; Huffman, J. C. J. Org. Chem. 1985, 50, 3095-3103.
6054 J. Org. Chem., Vol. 71, No. 16, 2006

PhotoactiVation of Amino-Substituted 1,4-Benzoquinones
SCHEME 3
(Figure 1A). The new absorption bands were assigned to
o-quinone methide 5 and were similar to those of other
o-quinone methide intermediates.13 When the photolysates were
warmed to 20 °C, the 339 and 455 nm bands slowly disappeared,
and the rate of disappearance was found to substantially increase
upon addition of 8 × 10-3 M dimethylaminocyclohexenone 12,
consistent with the above trapping experiments. In 30%
phosphate buffer in CH3CN at pH 6.95 as the medium, the
observed decay of the 339 nm absorption band was fit to pseudo-
first-order kinetics (Figure 1B), which gave an estimate for the
half-life of 5 of 34.9 ( 0.4 min at 20 °C (R2 ) 0.9991, 95%
confidence interval). This value for the half-life supersedes our
previously reported3 half-life for 5, which was miscalculated.
Pseudo-first-order decay kinetics would be consistent with
disappearance of the o-quinone methide 5 by a hydration
reaction.12,14
-
results were obtained upon photolysis of 3 (LG- ) PhCO2
with 542 nm light that had been passed through a monochro-
mator.
)
Nanosecond laser flash photolysis experiments were per-
formed in attempts to determine the rate constant for formation
of o-quinone methide from 3 (LG- ) PhCO2-), since this would
reflect the leaving group release rate. However, we were unable
to detect the 339 nm absorption of 5 upon 265 nm nanosecond
laser flash photolysis of 3 (LG- ) PhCO2-). Evidently 5 was
formed too slowly for the time resolution of our instrument. In
addition, the quantum yield for 5 could be too low to give a
detectable signal. We also attempted to monitor the kinetics of
the proton release step using the previously reported time-
resolved pH jump method.15c,d Although photolysis of 2.74 ×
10-4 M 3 (LG- ) PhCO2-) in 30% aq CH3CN to complete
conversion caused a decrease in the 620 nm absorption of the
bromocresol green, no signal for bleaching of this band could
be detected in the 355 nm laser flash photolysis experiment.
To trap the o-quinone methide 5 intermediate, photolyses were
conducted with various alkenes. Irradiation of 10-2 M 3 (LG-
) PhCO2-, PhCH2CO2-, 4-CNC6H4CO2-) with 0.1 M 3-(di-
methylamino)cyclohexen-1-one 12 in 30% aqueous CH3CN
produced the cycloadduct 13 (Scheme 3). The cycloadduct was
isolated chromatographically and identified by 1H and 13C NMR
analyses and Elemental Analysis. The structure was confirmed
by X-ray crystallography. The yields of the carboxylic acids
produced in these photolyses were 89-92%, and the cycloadduct
13 was produced in 79-87% yields at 100% conversions of
the reactants. Other alkene trapping reagents for o-quinone
methides,12 such as dihydropyran, ethyl vinyl ether, methyl
trimethylsilyl dimethylketene acetal, and diethyl fumarate, were
insufficiently reactive in trapping the o-quinone methide, which
is deactivated by multiple electron-releasing substituents, and
the photolyses of 3 gave essentially the same results as those
conducted without the added trapping reagent.
Photocyclization to Benzoxazolines 4. Phenolate derivatives
of 3 (LG- ) 4-YC6H4O-, Y ) H, CF3, CN) underwent
photocyclization under nonaqueous conditions, and the corre-
sponding benzoxazoline photoproducts 4 (LG- ) 4-YC6H4O-,
Y ) H, CF3, CN) were sufficiently stable to be isolated.
However, under aqueous conditions at neutral or basic pH these
benzoxazolines were unstable with respect to elimination of the
para-substituted phenolate groups (vide infra).
Photolysis of 10-2 M 3 (LG- ) PhO-) in CD2Cl2 or CD3-
CN with a sunlamp gave the photocyclization product, benzox-
azoline 4 (LG- ) PhO-), as the sole photoproduct in 100%
yield after complete conversion of the reactant (Scheme 1)
according to 1H NMR analyses with DMSO as an NMR
standard. In preparative-scale photolyses, no further purification
of 4 (LG- ) PhO-) was necessary after evaporation of the
solvent upon completion of the photolyses. Similarly, photolyses
of 3 (LG- ) 4-YC6H4O-, Y ) CF3, CN) gave 100% yields of
NMR pure 4 (LG- ) 4-YC6H4O-, Y ) CF3, CN) at 100%
conversions of the reactants.
The quantum yields for disappearance of 10-3 M 2-pyrroli-
dino-1,4-benzoquinones 3 (LG- ) PhCH2CO2-, PhCO2
-
,
4-CNC6H4CO2-) in the presence of 0.1 M 12 were determined
at 458 nm in air-saturated 30% aq CH3CN. These quantum
yields for disappearance should approximately equal the quan-
tum yields for formation of the carboxylic acids because the
acids are produced in ca. 90% yields when 12 is present to
prevent trapping of o-quinone methide 5 by the reactant (vide
supra). The values for Φdis were 0.005-0.006 for the three
carboxylate derivatives, whereas without added 12, higher values
(Φdis ) 0.007-0.008) were found. In the case of 3 (LG-
)
PhCO2-), the quantum yield for the appearance of the benzoic
acid, determined by HPLC analyses, was the same as Φdis. In
addition, for 3 (LG- ) PhCH2CO2-) the quantum yield was
unchanged upon purging the sample with argon.
The quantum yields for photocyclization of 3 (LG- ) PhO-)
to give benzoxazoline 4 (LG- ) PhO-), irradiating at 458 nm,
were determined in the air-saturated solvents CH2Cl2 and CH3-
Spectroscopic Studies. Spectroscopic evidence for the
formation of o-quinone methide intermediate 5 during photolyses
of 5 × 10-4 M 3 (LG- ) PhCO2-) in 30% aqueous CH3CN
was obtained by absorption spectroscopy. The photolyses were
conducted with a sunlamp, maintaining the sample at 2 °C, and
the experiment was repeated using 542 nm light passed through
a monochromator. In both experiments new absorption bands
were observed at 339 and 455 nm, along with residual absorption
of unreacted quinone 3 at 542 nm, after 30 min of photolysis
(13) Diao, L.; Yang, C.; Wan, P. J. Am. Chem. Soc. 1995, 117, 5369-
5370.
(14) (a) Chiang, Y.; Kresge, A. J.; Zhu, Y. J. Am. Chem. Soc. 2001,
123, 8089-8094. (b) Chiang, Y.; Kresge, A. J.; Zhu, Y. J. Am. Chem. Soc.
2000, 122, 9854-9855.
(15) (a) Ma, C.; Steinmetz, M. G.; Cheng, Q.; Jayaraman, V. Org. Lett.
2003, 5, 71-74. (b) Ma, C.; Steinmetz, M. G. Org. Lett. 2004, 6, 629-
632. (c) Ma, C.; Steinmetz, M. G.; Kopatz, E. J.; Rathore, R. Tetrahedron
Lett. 2005, 46, 1045-1048. (d) Ma, C.; Steinmetz, M. G.; Kopatz, E. J.;
Rathore, R. J. Org. Chem. 2005, 70, 4431-4442.
(12) Wan, P.; Barker, B.; Diao, L.; Fischer, M.; Shi, Y.; Yang, C. Can.
J. Chem. 1996, 74, 465-475.
J. Org. Chem, Vol. 71, No. 16, 2006 6055

Chen and Steinmetz
FIGURE 1. (A) Absorption spectrum of 3 (LG- ) C6H5CO2-) before photolysis in 30% aq CH3CN (- - -) at 2 °C and after photolysis (s), upon
warming to 20 °C; scans after photolysis show changes in absorbance at 10 min time intervals. (B) Pseudo-first-order fit of the decay of the
absorbance at 339 nm in 30% phosphate buffer in CH3CN at pH 6.95 at 20 °C.
rolidine to trichloroquinone 1616 (eq 5). Dichloroquinone 14
was obtained as the major regioisomer, as established by X-ray
crystallography. The minor regioisomer was thought to be 17,
which was not photolyzed due to its low yield.
TABLE 1. Quantum Yields for Photocyclization of
Amino-1,4-benzoquinones 3, 14, and 1 To Give Benzoxazolines,
Irradiating at 458 nm
Φ, solvent
b
reactant
30% aq CH3CNa
CH3CNb
CH2Cl2
3 (LG- ) OPh)
ndc
0.007
0.003
0.040
0.031
0.024
0.10
0.090
0.074
1
14
a Quantum yields of disappearance of the quinones, determined by
absorption spectroscopy. b Quantum yields of appearance of benzoxazoline
1
photoproduct determined by H NMR spectroscopy. c Not determined.
Elimination Reactions of Benzoxazolines 4. Under aqueous
conditions, the benzoxazolines 4 (LG- ) 4-YC6H4O-, Y ) H,
CF3, CN) underwent elimination of the para-substituted phe-
nolate leaving groups at neutral or basic pH. For example, the
loss of phenol from 4 (LG- ) PhO-) was observed by 1H NMR
spectroscopy at pD 7 in 30% phosphate buffer in CD3CN. At
17 °C first-order kinetics were observed with a lifetime of 13.1
h (τ1/2 ) 9.1 h), whereas at the more acidic pD of 5.6, the
benzoxazoline showed no sign of undergoing elimination phenol
(vide infra). Under nonaqueous conditions in CD2Cl2 or CD3-
CN, the eliminations of phenol could be effected by adding Et3N
to the solutions of 4 (LG- ) PhO-).
CN. The quantum yields decreased with increasing polarity of
the solvent (Table 1).
To determine whether the solvent effects on quantum yields
for cyclization of 3 (LG- ) PhO-) are general for 2-amino-
1,4-benzoquinones, we compared the solvent effects on quantum
efficiencies for 2-pyrrolidino-1,4-benzoquinone 1 (eq 1), which
was reinvestigated,2 and the photocyclization of dichloro-1,4-
benzoquinone 14 (eq 4). In addition to determining the quantum
We investigated whether the elimination of phenol would be
observed during a photolysis of 3 (LG- ) PhO-) that produced
4 (LG- ) PhO-) under the same buffered conditions as above
(Figure 2). Accordingly, benzoxazoline 4 (LG- ) PhO-) was
produced in 73% yield along with 2.7% of 11 (LG- ) PhO-)
and 8% of phenol at 86% conversion at pD 7, whereas at pD
5.6 the benzoxazoline 4 (LG- ) PhO-) was produced in 100%
yield at complete conversion of the reactant. From the data at
pD 7 (Figure 2), it was evident that the phenol produced by
photolysis could be accounted for by “dark” elimination of 4
(LG- ) PhO-). While monitoring this photolysis by 1H NMR
spectroscopy, broad peaks were also observed which suggested
the accompanying formation of high molecular weight material
which could not be readily identified.
yields (Table 1), preparative photolysis of 0.037 M 2-pyrroli-
dino-1,4-benzoquinone 1 in CH2Cl2 was conducted, and ben-
zoxazoline 2 was obtained in 73% isolated yield after silica gel
chromatography and crystallization. Preparative photolysis of
14 gave benzoxazoline 15 in 100% yield at 100% conversion
1
of reactant, according to H NMR analyses of the photolysate
with DMSO as a standard.
It should be noted that the synthesis of 3,5-dichloro-2-
pyrrolidino-1,4-benzoquinone 14 involved the addition of pyr-
(16) Wallenfels, K.; Hofmann, D.; Kern, R. Tetrahedron, 1965, 21,
2231-2237.
6056 J. Org. Chem., Vol. 71, No. 16, 2006

PhotoactiVation of Amino-Substituted 1,4-Benzoquinones
clization of 3 (LG- ) PhO-) to benzoxazoline is 0.10 in CH2-
Cl2, lower efficiency is observed for photolysis in the more polar
solvent, CH3CN. Pronounced decreases in efficiencies with polar
solvents are also observed for the other 2-pyrrolidino-1,4-
benzoquinones 1 and 14 (Table 1). The decreased quantum
efficiencies in going to polar solvents imply the involvement
of an intramolecular charge transfer (ICT) excited state17-19 in
the photochemical formation of the benzoxazolines. As shown
in Scheme 4, the initial ICT excited state would be subject to
rapid back electron transfer (bet) to regenerate the ground state
reactant upon stabilization of this excited state in polar solvents.
The bet could be competing with the hydrogen transfer step
that would be required to ultimately form the cyclized product
4.
It is possible that the immediate precursor in the photocy-
clization to benzoxazoline 4 is zwitterionic in character in the
ground state, as with structure 19 in Scheme 4. Evidence from
studies of the photochemistry of R-keto amides bearing leaving
groups at the position R to the keto group15 shows that
intermediates analogous to 19 can cyclize as well as expel
phenolate and carboxylate leaving groups. However, in the
photochemistry of 2-pyrrolidino-1,4-benzoquinone 3 it is not
necessary to postulate 19 in the elimination of phenolate groups,
since the formation of the phenols can be accommodated
satisfactorily by elimination from the benzoxazoline photoprod-
ucts 4. Unclear is the mechanism for elimination of carboxylate
leaving groups to form ortho-quinone methide 5, since the
elimination could occur either from 19 or 4. No evidence could
be obtained to support the direct elimination of carboxylate
leaving groups from 19 using nanosecond laser flash photolysis
FIGURE 2. Concentration versus time profile for photolysis of 3 (LG-
) PhO-) in 30% phosphate buffer in CD3CN at pD 7.
methods.
If the unobserved benzoxazolines 4 (LG- ) PhCH2CO2
,
-
PhCO2-, and 4-CNC6H4CO2-) are produced upon photolysis
of 3, one can predict the release rates of the carboxylate groups
from the Figure 3 plot of log k vs -pKa, which pertains to
eliminations of phenolate leaving groups at 17 °C. Extrapolation
of the data to the respective carboxylates gives release times of
115, 89, and 20 ms.
The estimated release times for carboxylate leaving groups
assume that the para-substituted phenolate leaving groups and
the carboxylate leaving groups lie on the same Bronsted-type
correlation line in the plot of log k vs -pKa. Both phenols and
carboxylic acids are well-correlated in Bronsted plots for general
acid-catalyzed dehydration of acetaldehyde hydrate20 and as
conjugate bases in proton transfer from acetylacetone.21 More
diverse bases are correlated in Bronsted plots for general base-
catalyzed deprotonation of ethyl nitroacetate22a and detritiation
of tert-butylmalononitrile-1-t.22b Nevertheless, correlations in-
volving different chemical classes of acids or bases can be a
source of scatter in Bronsted-type plots,23 and therefore, the
FIGURE 3. Plot of log k vs -pKa for the release of 4-YC6H4OH (Y
) H, CF3, CN) from 4 in 30% phosphate buffer at 17 °C.
The kinetics for the release of the para-substituted phenolic
groups from 4 dissolved in 30% phosphate buffer in CD3CN
(pD 7) at 17 °C were then monitored by 1H NMR spectroscopy
to obtain the rate constants for the release of 4-YC6H4OH (Y
) CF3, CN). The lifetimes (1/krelease) for the release of 4-YC6H4-
OH (Y ) CF3, CN) were found to be 0.54 and 0.13 h,
respectively. With the kinetic data for phenol included (vide
supra), the linear equation log k (h-1) ) 0.998(-pKa) + 8.80
gave a best fit to the data (Figure 3).
(17) Bruce, J. M. In The Chemistry of Quinonoid Compounds; Patai, S.,
Ed.; John Wiley & Sons: New York, 1974; Part 1, p 472.
(18) An analogous intermolecular electron transfer occurs from triethyl-
amine to the benzophenone triplet excited state: Peters, K. S.; Shaefer, C.
G. J. Am. Chem. Soc. 1980, 102, 7566-7567.
Discussion
2-Pyrrolidino-1,4-benzoquinones 3 bearing phenolate leaving
groups photocyclize to benzoxazolines 4 (LG- ) 4-YC6H4O-,
Y ) H, CF3, CN) upon exposure to light in the 460-650 nm
wavelength region. Chemical yields of 4 (LG- ) 4-YC6H4O-,
Y ) H, CF3, CN) are 100% at complete conversion of the
photochemical reactants 3 (LG- ) 4-YC6H4O-, Y ) H, CF3,
CN) when the photolyses are conducted in CH2Cl2 or CH3CN
as the solvents. Although the quantum yield for the photocy-
(19) Jones, G.; Qian, X. J. Phys. Chem. 1998, 102, 2555-2560.
(20) (a) Ritchie, C. D. Physical Organic Chemistry; Marcel Dekker: New
York, 1990; p 237. (b) Bell, R. P.; Higginson, W. C. E. Proc. R. Soc.
London. Ser. A 1949, 197, 141-159. (c) Bell, R. P. The Proton in Chemistry;
Cornell University Press: Ithaca, NY, 1959; pp 174-175.
(21) Ahrens, V. M.-L.; Eigen, M.; Kruse, W.; Maass, G. Ber. Bunsen-
Ges. Phys. Chem. 1970, 74, 380-385.
(22) (a) Barnes, D. J.; Bell, R. P. Proc. R. Soc. London. Ser. A 1970,
318, 421-440. (b) Pratt, R. F.; Bruice, T. C. J. Org. Chem. 1972, 37, 3563-
3564.
J. Org. Chem, Vol. 71, No. 16, 2006 6057

Chen and Steinmetz
SCHEME 4
Preparation of 2-Hydroxy-5-methoxy-3,6-dimethylbenzene-
methanol (9). The procedure was similar to one reported in the
literature.24 To a solution of 2.0 g (11 mmol) of benzaldehyde 8 in
20 mL of glacial acetic acid was added 1.7 g (44 mmol) of solid
NaBH4 in portions with cooling to 16-21 °C. After 2 h, 10 mL of
water was added and the mixture was neutralized with aq NaHCO3.
The mixture was extracted with ethyl acetate, and the extracts were
dried over MgSO4 and concentrated in vacuo. The solid residue
was crystallized from 10% ethyl acetate in hexane to give 1.06 g
(52% yield) of colorless crystals: mp 75.5-77.0 °C. The spectral
data were as follows: 1H NMR (CDCl3) δ 2.02 (s, 3 H), 2.18(s, 3
H), 3.24(s, broad, 1 H), 3.73 (s, 3 H), 4.79 (s, 2 H), 6.58 (s, 1 H),
7.57 (s, broad,1 H); 13C NMR(CDCl3) δ 11.5, 16.8, 56.7, 60.8,
113.5, 121.7, 122.5, 123.8, 148.2, 150.6. Anal. Calcd for
C10H14O3: C, 65.92; H, 7.74. Found: C, 65.81; H, 7.57.
Preparation of 2-Hydroxymethyl-3,6-dimethyl-2,5-cyclohexa-
diene-1,4-dione (10). A procedure similar to one in the literature
was followed.25 To 2.0 g (1.0 mmol) of 2-hydroxy-5-methoxy-3,6-
dimethylbenzenemethanol 9 in 10 mL of CH3CN was added
dropwise, with stirring, a solution of 18.0 g (33.0 mmol) Ce(NH4)2-
(NO3)6 in 100 mL of deionized water with cooling in an ice bath.
After being stirred overnight at room temperature, the mixture was
extracted with CHCl3, washed with saturated NaCl, dried over
MgSO4, and concentrated in vacuo. MPLC of the residue, eluting
with 50% EtOAc in hexane, gave crystalline product, which was
crystallized from 10% EtOAc in hexane to obtain 1.63 g (63%) of
yellow crystals, mp 52.0-53.5 °C. The spectral data were as
follows: 1H NMR (CDCl3) δ 2.02 (d, J ) 1.5 Hz, 3 H), 2.06 (s, 3
H), 4.53 (s, 2 H), 6.59 (q, J ) 1.5 Hz, 1 H); 13C NMR (CDCl3) δ
11.8, 15.9, 57.5, 133.6, 140.7, 142.1, 145.5, 187.7, 188.6. Anal.
Calcd for C9H10O3: C, 65.05; H, 6.07. Found: C, 64.72; H, 6.11.
Preparation of 2-Hydroxymethyl-3,6-dimethyl-5-pyrrolidino-
2,5-cyclohexadiene-1,4-dione (6). A procedure similar to one
reported in the literature was followed.1b To 1.5 g (9.0 mmol) of
2-hydroxymethyl-3,6-dimethyl-2,5-cyclohexadiene-1,4-dione 10 in
100 mL of CH2Cl2 was added dropwise with stirring a solution of
1.5 mL (18.0 mmol) of pyrrolidine in 20 mL of CH2Cl2 with cooling
in an ice bath, while keeping the reaction in the dark. After 3 h at
room temperature, the volatiles were removed in vacuo. MPLC of
the residue, eluting with 50% EtOAc in hexane, gave 1.42 g (67%)
of the purple product as a viscous oil. The spectral data were as
follows: 1H NMR (CDCl3) δ 1.84 (m, 4 H), 1.94 (s, 3 H), 1.98 (s,
3 H), 3.40 (s, broad, 1 H), 3.63 (m, 4 H), 4.47 (s, 2 H); 13C NMR
(CDCl3) δ 11.4, 12.9, 26.0, 53.4, 59.0, 111.3, 136.7, 141.0, 151.0,
186.9, 187.8.
release times for carboxylates leaving groups, as predicted from
the Bronsted-type plot for elimination of para-substituted
phenolates (Figure 3), will be subject to unknown error, because
the carboxylate and phenolate leaving groups are dissimilar
leaving group bases.
Conclusion
2-Pyrrolidino-1,4-benzoquinones 3 photocyclize to benzox-
azolines 4 upon exposure to visible light in the 450-650 nm
wavelength region. Quantum efficiencies decrease with increas-
ing solvent polarity, consistent with significant intramolecular
charge transfer character in the initial excited state. Benzox-
azoline photoproducts with acyloxymethyl or phenoxymethyl
substitution at the C-7 position are unstable with respect to
elimination of the carboxylate or phenolate leaving groups in
aqueous media at neutral or basic pH. Carboxylate groups are
expelled rapidly to form an ortho-quinone methide intermediate,
whereas with a less labile phenolate leaving group the benzox-
azoline is observed to build up as a photoproduct under aqueous
conditions and can be isolated after photolyses of 3 (LG-
)
4-YC6H4O-, Y ) H, CF3, CN) performed in nonhydroxylic
solvents. Rate constants for elimination of para-substituted
phenolate leaving groups from benzoxazolines give linear plots
of log k vs -pKa in aqueous media under buffered conditions.
Experimental Section
Preparation of 2-Hydroxy-5-methoxy-3,6-dimethylbenzalde-
hyde (8). The procedure was similar to one reported in the
literature.7 To a mixture of 5.0 g (32.8 mmol) of 2,5-dimethyl-4-
methoxyphenol8 in 300 mL of CH3CN (distilled over CaH2)
containing 13 mL (93.3 mmol) of triethylamine and 9.8 g (103
mmol) of anhydrous MgCl2 was added 3.5 g (117 mmol) of dry
paraformaldehyde in portions. The mixture was refluxed for 8 h
and cooled, 5% aqueous HCl was added, and the mixture was
extracted with ether. The extracts were dried over MgSO4 and
concentrated in vacuo, and the residue was purified by medium-
pressure liquid chromatography on 230-400 mesh silica gel
(MPLC), eluting with 10% EtOAc in hexane. This gave 3.67 g
(62% yield) of yellow crystals, mp 94.5-95.5 °C. The spectral data
were as follows: 1H NMR (CDCl3) δ 2.20 (s, 3 H), 2.42 (s, 3 H),
3.76 (s, 3 H), 6.98 (s, 1 H), 10.29 (s, 1 H), 11.73 (s, 1 H); 13C
NMR (CDCl3) δ 9.8, 15.6, 57.3, 118.1, 123.8, 124.5, 126.9, 149.4,
155.5, 195.9.
(24) Nieminen, T. E. A.; Hase, T. A. Tetrahedron Lett. 1987, 28, 4725-
4728.
(23) For a good discussion of scatter and nonlinearity in Bronsted plots,
see: Bordwell, F. G.; Hughes, D. L. J. Org. Chem. 1982, 47, 3224-3232.
(25) Tohma, H.; Morioka, H.; Harayama, Y.; Hashizume M.; Kita, Y.
Tetrahedron Lett. 2001, 42, 6899-6902.
6058 J. Org. Chem., Vol. 71, No. 16, 2006

PhotoactiVation of Amino-Substituted 1,4-Benzoquinones
Preparation of Carboxylate Derivatives 3 (LG- ) PhCO2
-
,
The spectral data for 2,5-dimethyl-3-[(4-trifluoromethylphenoxy)-
methyl]-6-pyrrolidino-2,5-cyclohexadiene-1,4-dione 3 (LG-
PhCH2CO2-, 4-CNC6H4CO2-) of 2-Hydroxymethyl-3,6-dimeth-
yl-5-pyrrolidino-2,5-cyclohexadiene-1,4-dione. To a solution of
40 mmol of 2-hydroxymethyl-3,6-dimethyl-5-pyrrolidino-2,5-cy-
clohexadiene-1,4-dione 6 in 100 mL of CH2Cl2 in an ice bath was
added dropwise with stirring a solution of 80 mmol of acid chloride
in 20 mL of CH2Cl2. The mixture was stirred at room temperature
for 10-30 h, depending on the ester to be synthesized. In each
case, the mixture was washed with 5% aq HCl and satd NaCl, dried
over MgSO4, and concentrated in vacuo. MPLC of the residue,
eluting with 30% EtOAc in hexane gave each ester product as purple
crystals, generally in 70-80% yields.
)
4-CF3C6H4O-) were as follows: 1H NMR (CD3CN) δ 1.83 (m, 4
H), 2.01 (s, 3 H), 2.02 (s, 3 H), 3.63 (m, 4 H), 5.00 (s, 2 H), 7.08
(d, J ) 9.0 Hz, 2 H), 7.61 (d, J ) 9.0 Hz, 2 H); 13C NMR (CD3-
CN) δ 12.5, 13.2, 26.4, 53.9, 62.5, 111.4, 123.2 (q, J ) 33 Hz),
125.7 (q, J ) 272 Hz), 128.0 (q, J ) 4 Hz), 137.6, 142.8, 152.2,
162.5, 184.5, 188.6.
General Procedure for Photolyses of Compound 1, 14, and
3 (LG- ) PhCO2-, PhCH2CO2-, 4-CNC6H4CO2-, PhO-,
4-CF3C6H4O-, and 4-CNC6H4O-). A tube containing 0.02-0.03
M 1, 3, or 14 in 30% H2O in CH3CN, CH2Cl2, or CH3CN, mounted
inside a Pyrex beaker, was irradiated with a 120 W sunlamp through
the walls of the beaker, maintaining the sample at room temperature
with a stream of air. Photolyses at 542 nm were conducted by
photolyzing samples with light from a 200 W high-pressure mercury
lamp, which was passed through a monochromator. Details of
specific photolyses are given below.
Photolyses of 3,6-Dimethyl-2-pyrrolidino-2,5-cyclohexadiene-
1,4-dione 1. A solution of 232 mg (1.1 mmol) of 2-pyrrolidino-
1,4-benzoquinone 1 in 30 mL of CH2Cl2 was irradiated using the
general photolyses procedure. The solvent was removed in vacuo.
MPLC of the residue, eluting with 20% EtOAc in hexane, gave
crystalline product, which was crystallized from 10% EtOAc in
hexane to obtain 170 mg (73% yield) of cyclization product 2 as
white crystals, mp 110.0-111.5 °C. The spectral data for 1,2,3,3a-
tetrahydro-5,8-dimethylpyrrolo[2,1-b]benzoxazole 2 were as fol-
lows: 1H NMR (CDCl3) δ 1.87 (m, 2 H), 2.07 (s, 3 H), 2.14 (s, 3
H), 2.21 (m, 2 H), 2.97 (m, 1 H), 3.35 (m, 1 H), 5.15 (br s, 1 H),
5.81 (t, J ) 3.3 Hz, 1 H), 6.61 (s, 1 H); 13C NMR (CDCl3) δ 10.8,
15.3, 24.2, 32.8, 55.8, 102.8, 110.8, 111.1, 115.2, 140.5, 145.0,
148.3.
The spectral data for 2-[(benzoyloxy)methyl]-3,6-dimethyl-5-(1-
pyrrolidino)-2,5-cyclohexadiene-1,4-dione 3 (LG ) PhCO2-) were
as follows: 1H NMR (CDCl3) δ 1.85 (m, 4 H), 2.03 (s, 3 H), 2.08
(s, 3 H), 3.63 (m, 3 H), 5.26 (s, 4 H), 7.38 (t, J ) 7.2 Hz, 2 H),
7.51 (t, J ) 7.2 Hz, 1 H), 798 (d, J ) 7.2 Hz, 2 H); 13C NMR
(CDCl3) δ 12.8, 13.5, 26.1, 53.3, 58.5, 112.1, 128.4, 129.8, 129.9,
133.1, 137.1, 141.1, 150.3, 166.3, 183.9, 187.4; absorption (30%
aq CH3CN) λmax 542 nm (ꢀ 3150 M-1 cm-1). Anal. Calcd for
C20H21O4N: C, 70.78; H, 6.24; N, 4.13; Found: C, 70.88; H, 6.35;
N, 4.12.
The spectral data for 2-[(phenylacetyloxy)methyl]-3,6-dimethyl-
5-(1-pyrrolidino)-2,5-cyclohexadiene-1,4-dione 3 (LG ) PhCH2CO2-)
were as follows: 1H NMR (CDCl3) δ 1.85 (m, 4 H), 1.92 (s, 3 H),
2.02 (s, 3 H), 3.60 (s, 2 H), 5.03 (s, 2 H), 7.25 (m, 5 H); 13C NMR
(CDCl3) δ 12.3, 13.4, 26.1, 41.3, 53.3, 58.5, 112.2, 127.2, 128.6,
129.4, 133.89, 136.90, 141.1, 171.3, 183.9, 187.3; absorption (30%
aq CH3CN) λmax 542 nm (ꢀ 2850 M-1 cm-1). Anal. Calcd for
C21H23O4N: C, 71.37; H, 6.56; N, 3.96. Found: C, 71.17; H, 6.51;
N, 3.84.
The spectral data for 2-[(4-cyanobenzoyloxy)methyl]-3,6-di-
methyl-5-(1-pyrrolidino)-2,5-cyclohexadiene-1,4-dione 3 (LG )
4-CNC6H4CO2-) were as follows: 1H NMR (CDCl3) δ 1.86 (m, 4
H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.64 (m, 4 H), 5.28 (s, 2 H), 7.07
(d, J ) 8.7 Hz, 2 H), 8.10 (d, J ) 8.6 Hz, 2 H); 13C NMR (CDCl3)
δ 12.5, 13.4, 26.1, 53.4, 59.2, 112.0, 116.5, 118.1, 130.3, 132.3,
133.8, 136.5, 141.4, 150.4, 164.7, 183.8, 187.2; absorption (30%
aq CH3CN) λmax 542 nm (ꢀ 2990 M-1 cm-1). Anal. Calcd for
C21H20O4N2O4: C, 69.22; H, 5.53; N, 7.69. Found: C, 68.97; H,
5.58; N, 7.59.
Photolyses of 2,6-Dichloro-5-methyl-3-pyrrolidino-2,5-cyclo-
hexadiene-1,4-dione 14. Irradiation of 16 mg of 14 in 0.45 mL of
CD2Cl2 in a NMR tube to 100% conversion produced NMR pure
1,2,3,3a-tetrahydro-5,7-dichloro-8-methylpyrrolo[2,1-b]benzox-
azole 15. The yield was 100%, determined by NMR using a known
amount of DMSO as a NMR standard. The spectral data for 15
were as follows: 1H NMR (CDCl3) δ 1.86 (m, 2 H), 2.15(s, 3 H),
2.22 (m, 2 H), 3.18 (m, 1 H), 3.38 (m, 1 H), 5.51 (br s, 1 H), 5.89
(m, 1 H).
Preparation of 4-Cyanophenolate Derivative 3 (LG-
)
Photolysis of 2-[(Benzoyloxy)methyl]-3,6-dimethyl-5-(1-pyr-
rolidino)-2,5-cyclohexadiene-1,4-dione 3 (LG- ) PhCO2-).
Irradiation of 0.43 g (1.3 mmol) of 3 (LG ) PhCO2-) in 50 mL of
30% aq CH3CN to 100% conversion produced adduct 11 as a ca.
1:1 mixture of diastereomers. The solution was extracted with ethyl
acetate. Adduct 11 was separated by MPLC, eluting with 20% ethyl
acetate in hexane, to obtain 0.25 g (36% yield) of a viscous oil.
The spectral data for 11 were as follows (nonoverlapping minor
diastereomer peaks in parentheses): 1H NMR (CDCl3) δ 1.40 (s,
3 H), 1.44 (s, 3 H), 1.68 (m, 8 H), 1.86 (s, 6 H), 1.85 (m, 4 H),
2.13 (s, 3 H), 2.15 (s, 3 H), 2.17 (m, 4 H), 2.19 (s, 3 H), 2.20 (s,
3 H), 2.45 (m, 2 H), 2.73 (m, 6 H), 2.88 (m, 4 H), 2.99 (m, 2 H),
3.34 (m, 2 H), 5.23 (d, J ) 12 Hz, 2 H), 5.32 (d, J ) 12 Hz, 2 H),
5.76 (m, 2 H), 7.41 (t, J ) 7.8 Hz, 4 H), 7.54 (t, J ) 7.8 Hz, 2 H),
7.95 (d, J ) 7.8 Hz, 4 H); 13C NMR (CDCl3) δ 10.7 (10.6), 11.6,
13.2 (13.1), 17.9 (17.8), 24.1, 25.0 (24.9), 32.61 (32.58), 36.6, 48.0
(47.9), 52.3 (52.0), 55.9 (55.8), 58.6, 94.94 (94.92), 102.6, 110.9
(110.8), 112.0 (111.8), 112.5, 128.7, 129.8, 133.5, 138.98 (138.96),
139.3, 145.0 (144.8), 145.6 (145.5), 146.9 (146.7), 166.2, 193.8
(193.4), 199.1. Anal. Calcd for C33H36N2O6: C, 71.15; H, 6.52; N,
5.03. Found: C, 70.76; H, 6.58; N, 4.99.
4-CNC6H4O-) of 2-Hydroxymethyl-3,6-dimethyl-5-pyrrolidino-
2,5-cyclohexadiene-1,4-dione. The procedure followed one reported
previously.26 To a solution of 71.5 mg (0.60 mmol) of 4-cyanophe-
nol, 0.10 g (0.43 mmol) of 2-hydroxymethyl-3,6-dimethyl-5-
pyrrolidino-2,5-cyclohexadiene-1,4-dione 6, and 0.21 g (0.80 mmol)
of Ph3P in 5 mL of dry DMF was added 139 mg (0.13 mL, 0.80
mmol) of diethyl azodicarboxylate dropwise via pipet under nitrogen
while cooling in an ice bath. The mixture was stirred overnight.
The mixture was concentrated in vacuo, and 20 mL of ethyl acetate
was added along with 20 mL water. The phases were separated,
and the aqueous was extracted twice with ethyl acetate. The
combined organic phases were dried over Na2SO4 and concentrated
in vacuo. MPLC of the residue, eluting with 10% ethyl acetate in
hexane, gave 53 mg (37% yield) of NMR pure 4-cyanophenoxy
derivative 3 (LG- ) 4-CNC6H4O-) as a purple oil. The spectral
data for 2,5-dimethyl-3-[(4-cyanophenoxy)methyl]-6-pyrrolidino-
2,5-cyclohexadiene-1,4-dione 3 (LG- ) 4-CNC6H4O-) were as
follows: 1H NMR (CD3CN) δ 1.84 (m, 4 H), 2.00 (s, 3 H), 2.01
(s, 3 H), 3.63 (m, 4 H), 5.01 (s, 2 H), 7.08 (d, J ) 9.0 Hz, 2 H),
7.65 (d, J ) 9.0 Hz, 2 H).
Preparation of 4-Trifluoromethylphenolate Derivative 3 (LG-
) 4-CF3C6H4O-) of 2-Hydroxymethyl-3,6-dimethyl-5-pyrroli-
dino-2,5-cyclohexadiene-1,4-dione. The same procedure as for 3
(LG- ) 4-CNC6H4O-) was followed to obtain 54 mg (33% yield)
of NMR pure compound 3 (LG- ) 4-CF3C6H4O-) as a purple oil.
Photolysis of 2-[(Benzoyloxy)methyl]-3,6-dimethyl-5-(1-pyr-
rolidinyl)-2,5-cyclohexadiene-1,4-dione 3 (LG- ) PhCO2-) with
3-(Dimethylamino)cyclohexen-1-one 12 as Trapping Reagent.
Irradiation of 0.35 g (1.0 mmol) of 3 (LG ) PhCO2-) in 50 mL of
30% aq CH3CN with 0.1 M 3-(dimethylamino)cyclohexen-1-one
12 to 100% conversion produced cycloadduct 13. The solution was
extracted with ethyl acetate. Cycloadduct 13 was separated by
(26) Kraus, G. A.; Zhang, N. J. Org. Chem. 2000, 65, 5644-5646.
J. Org. Chem, Vol. 71, No. 16, 2006 6059

Chen and Steinmetz
MPLC, eluting with 20% ethyl acetate in hexane, to obtain 0.30 g
(87% yield) of crystalline solid, mp 194-196 °C. Cycloadduct 13
was characterized by NMR spectroscopy, elemental analysis, and
X-ray crystallography. The spectral data for 13 were as follows:
1H NMR (CDCl3) δ 1.08 (s, 3 H) 1.09 (s, 3 H) 1.86 (m, 2 H) 2.05
(s, 3 H) 2.16 (s, 3 H) 2.21 (m, 2 H) 2.29 (s, 2 H) 2.39 (s, 2 H) 2.93
(m, 1 H) 3.24 (m, 2 H) 3.34 (m, 1 H) 5.79 (m, 1 H); 13C NMR
(CDCl3) δ 10.8, 11.7, 20.1, 24.1, 28.6, 32.4, 32.7, 41.6, 50.9, 56.0,
102.9, 107.7, 111.5, 113.9, 114.4, 138.8. Anal. Calcd for C21H25-
NO3: C, 74.31; H, 7.42; N, 4.13. Found: C, 74.28; H, 7.56; N,
4.20.
Photolysis of 2,5-Dimethyl-3-phenoxymethyl-6-pyrrolidino-
2,5-cyclohexadiene-1,4-dione 3 (LG- ) PhO-). A solution of 15
mg (0.048 mmol) of 3 (LG- ) PhO-) in 0.45 mL of CD3CN in an
NMR tube was irradiated following the general procedure to obtain
NMR-pure cyclization compound, 1,2,3,3a-tetrahydro-5,8-dimethyl-
7-phenoxymethylpyrrolo[2,1-b]benzoxazole 4 (LG- ) PhO-). The
yield was 100%, determined by NMR using a known amount of
DMSO as a NMR standard. The spectral data were as follows: 1H
NMR (CD3CN) δ 1.84 (m, 2 H), 2.09 (s, 3 H), 2.12 (s, 3 H), 2.22
(m, 2 H), 2.99 (m, 1 H), 3.32 (m,1 H), 5.03 (d, 2 H), 5.76 (m,1 H),
6.03 (br s, 1H), 6.95 (t, J ) 7.2 Hz, 1 H), 7.00 (d, J ) 7.2 Hz, 2
H), 7.30 (t, J ) 7.2 Hz, 2 H); 13C NMR (CD3CN) δ 11.5, 12.0,
24.5, 33.3, 56.2, 63.5, 103.3, 111.9, 115.6, 115.7, 116.9, 121.6,
130.5, 141.9, 146.1, 149.2, 159.9.
contained in a 10 cm × 1.8 cm quartz cylindrical cell of 25 mL
volume. Behind the photolysate was mounted a quartz cylindrical
cell containing 25 mL of actinometer. Light output was monitored
by ferrioxalate actinometry28 using the splitting ratio technique. To
ensure that all of the 458 nm light was absorbed, the concentration
of the Fe3+ in the actinometer solution was increased to 0.0154 M,
as prescribed by the literature.29 A third cell mounted behind the
main cell (in-line with the light beam) showed that all of the 458
nm light was always absorbed by the actinometer in the main cell.
The quantum yield was taken to be ΦFe ) 1.09.29 The product
2+
yields were determined by 1H NMR or HPLC analyses, and
absorption spectroscopy was used to monitor disappearance of
starting material.
General Procedure for Low-Temperature Photolyses. A 5 ×
10-4 M solution of 3 (LG ) PhCO2-) in 30% aq CH3CN or in
30% phosphate buffer in CH3CN at pH 7 was placed in a cell that
was mounted inside a Dewar, which had windows that allowed
photolyses to be conducted using a sunlamp or 542 nm light passed
through a monochromator. The temperature was maintained at 2
°C during photolysis with an ice bath. The purple color of 3
disappeared after 30 min. The ice bath was replaced by water, the
sample was warmed to 20 °C in 3 min, and the absorption spectrum
was obtained at 10 min time intervals.
General Procedure for Release Rate Determinations. Solu-
tions of 10-15 mg (ca. 0.04 mmol) of 3 (LG ) PhO-, 4-CNC6H4O-,
4-CF3C6H4O-) in 0.4-0.5 mL of CD2Cl2 in an NMR tube were
irradiated using the general photolysis procedure. After the purple
color of 3 disappeared, the solvent was removed in vacuo and 0.4-
0.5 mL of 30% phosphate buffer in CD3CN (pD 7) was added along
Photolyses of 2,5-Dimethyl-3-[(4-trifluoromethylphenoxy)-
methyl]-6-pyrrolidino-2,5-cyclohexadiene-1,4-dione 3 (LG-
)
4-CF3C6H4O-). Irradiation of 10.1 mg (0.030 mmol) of 3 (LG )
4-CF3C6H4O-) in 0.45 mL of CD3CN in a NMR tube to 100%
conversion produced NMR pure cyclization compound, 1,2,3,3a-
tetrahydro-5,8-dimethyl-7-[(4-trifluoromethylphenoxy)methyl]pyrrolo-
[2,1-b]benzoxazole 4 (LG- ) 4-CF3C6H4O-). The yield was 100%,
determined by NMR using a known amount of DMSO as a NMR
standard. The spectral data were as follows: 1H NMR (CD3CN) δ
1.83 (m, 2 H), 2.11(s, 3 H), 2.15 (s, 3 H), 2.05 (m, 1 H), 3.02(m,1
H), 3.35 (m, 1H), 5.12 (m, 2H), 5.79(m, 1H) 6.04 (s, 1H), 7.16 (d,
J ) 8.4 Hz, 2 H), 7.64 (d, J ) 8.4 Hz, 2 H); 13C NMR (CD3CN)
δ 11.5, 11.9, 24.5, 33.3, 56.2, 63.9, 103.4, 111.9, 115.9, 116.4,
116.6, 122.3 (q, J ) 32 Hz), 125.8 (q, J ) 271 Hz), 127.9 (q, J )
4 Hz), 142.2, 146.2, 149.2, 162.9.
1
with a standard amount of DMSO. The H NMR spectrum was
then obtained at certain time intervals to monitor the decay of
photoproduct 4, while maintaining the sample at 17 °C in the dark.
Acknowledgment. We thank Ms. Erica Kopatz and Prof.
Rajendra Rathore for assistance with the nanosecond laser flash
photolysis experiments and Dr. Sergey Lindeman for the X-ray
diffraction results on compounds 13 and 14. Acknowledgment
is made to the donors of the Petroleum Research Fund,
administered by the American Chemical Society, for support
of this research.
Photolyses of 2,5-Dimethyl-3-[(4-cyanophenoxy)methyl]-6-
pyrrolidino-2,5-cyclohexadiene-1,4-dione 3 (LG- ) 4-CNC6H4O-).
Irradiation of 11.4 mg (0.034 mmol) of 3 (LG ) 4-CNC6H4O-) in
0.45 mL of CD3CN in an NMR tube to 100% conversion produced
NMR-pure cyclization compound 1,2,3,3a-tetrahydro-5,8-dimethyl-
Supporting Information Available: Synthesis procedures of
2,5-dimethoxy-3,6-dimethylbenzenemethanol, 1-chloro-2,5-dimethoxy-
3,6-dimethylbenzene, 1-phenoxy-2,5-dimethoxy-3,6-dimethylben-
zene, 2,6-dimethyl-3-phenoxymethyl-2,5-cyclohexadiene-1,4-dione,
7-[(4-cyanophenoxy)methyl]pyrrolo[2,1-b]benzoxazole 4 (LG-
)
4-CNC6H4O-). The yield was 100%, determined by NMR using a
known amount of DMSO as a NMR standard. The spectral data
were as follows: 1H NMR (CD3CN) δ 1.83 (m, 2 H), 2.05 (m,
1H) 2.08 (s, 3 H), 2.12 (s, 3 H), 2.21 (m, 1 H), 5.10 (m, 1H), 5.77
(m, 1H) 6.00 (s, 1H), 7.12 (d, J ) 9.0 Hz, 2 H), 7.65 (d, J ) 9.0
Hz, 2H).
3 (LG- ) PhO-), 14, and 17. NMR spectral data for 2, 3 (LG-
)
PhCO2-, PhCH2CO2-, 4-CNC6H4CO2-, PhO-, 4-CNC6H4O-,
4-CF3C6H4O-), 4 (PhO-, 4-CNC6H4O-, 4-CF3C6H4O-), 6, 8-10,
11 (LG- ) PhCO2-), 13-15, 17, 2,5-dimethoxy-3,6-dimethylben-
zenemethanol, 1-chloro-2,5-dimethoxy-3,6-dimethylbenzene, 1-phe-
noxy-2,5-dimethoxy-3,6-dimethylbenzene, and 2,6-dimethyl-3-
phenoxymethyl-2,5-cyclohexadiene-1,4-dione. X-ray structure of 13
and 14 and CIF files for 13 and 14. This material is available free
of charge via the Internet at http://pubs.acs.org.
General Procedure for Product Quantum Yield Determina-
tions. The quantum yields were determined with a semi-micro-
optical bench apparatus that was similar to that described by
Zimmerman.27 Light from a 200 W high-pressure mercury lamp
was passed through an Oriel monochromator, which was set to 542
nm wavelength, and collimated through a lens. A fraction of the
light was diverted 90° by a beam splitter to a 10 cm × 3.6 cm side
quartz cylindrical cell containing actinometer. The photolysate was
JO060790G
(28) Hatchard, C. G.; Parker, C. A. Proc. R. Soc. London 1956, 235,
518-36.
(29) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photochem-
istry, 2nd ed.; Marcel Dekker: New York, 1993; pp 299-305.
(27) Zimmerman, H. E. Mol. Photochem. 1971, 3, 281-92.
6060 J. Org. Chem., Vol. 71, No. 16, 2006