Comparison of photoenolization and alcohol release from alkyl-substituted benzoyl benzoic esters

Article abstract of DOI:10.1139/V10-161

Photolysis of 1B in argon-saturated solutions yields 4B and releases methanol. Laser flash photolysis of 1B shows formation of biradical 2B, which has a lifetime of ～50 ns and a _max at 330 nm. Biradical 2B undergoes an intersystem crossing to form photoenols E-3B and Z-3B with a _max at 390 nm. Laser flash photolysis shows that the lifetimes of E-3B and Z-3B are affected by the solvent. Density functional theory calculations demonstrate that the transition-state barrier for a 1,5-H atom shift from Z-3B to regenerate 1B is affected by the ortho-alkyl substituents, whereas the stereoelectronics of the alkyl substituent affect the transition-state barrier of E-3B as it undergoes electrocyclic ring closure to form 4B. The photoreactivity of 1B was compared with its analogous methyl and isopropyl derivatives 1A and 1C, respectively,to better estimate the effect of the alkyl substituent on reactivity.

Full text of DOI:10.1139/V10-161

331
Comparison of photoenolization and alcohol
release from alkyl-substituted benzoyl benzoic
esters
Sivaramakrishnan Muthukrishnan, Tamara C.S. Pace, Qian Li, Brian Seok,
Gerdien de Jong, Cornelia Bohne, and Anna D. Gudmundsdottir
Abstract: Photolysis of 1B in argon-saturated solutions yields 4B and releases methanol. Laser flash photolysis of 1B
shows formation of biradical 2B, which has a lifetime of ~50 ns and a lmax at 330 nm. Biradical 2B undergoes an intersys-
tem crossing to form photoenols E-3B and Z-3B with a lmax at 390 nm. Laser flash photolysis shows that the lifetimes of
E-3B and Z-3B are affected by the solvent. Density functional theory calculations demonstrate that the transition-state bar-
rier for a 1,5-H atom shift from Z-3B to regenerate 1B is affected by the ortho-alkyl substituents, whereas the stereoelec-
tronics of the alkyl substituent affect the transition-state barrier of E-3B as it undergoes electrocyclic ring closure to form
4B. The photoreactivity of 1B was compared with its analogous methyl and isopropyl derivatives 1A and 1C, respectively,
to better estimate the effect of the alkyl substituent on reactivity.
Key words: photoremovable protecting groups, photoenols, laser flash photolysis, 1,5 H-atom shift, electrocyclic ring clo-
sure, intramolecular lactonization.
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Resume : La photolyse de 1B dans des solutions saturees en argon conduit a la formation de 4B et a la liberation de me-
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thanol. La photolyse eclair au laser de 1B conduit a la formation du biradical 2B dont le temps de vie est d’environ 50 ns
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et un lmax a 330 nm. Le biradical 2B subit une transformation intersysteme avec formation des photoenols E-3B et Z-3B
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avec un lmax a 390 nm. La photolyse eclair au laser montre que les temps de vie des isomeres E-3B et Z-3B sont affectes
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par le solvant. Des calculs selon la theorie de la fonctionnelle de la densite demontre que la barriere de l’etat de transition
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pour un deplacement 1,5 d’atome d’hydrogene a partir de Z-3B et conduisant a la regeneration du produit 1B est affectee
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par les substituants ortho-alkyles alors que les effets stereoelectroniques du substituant alkyle affectent la barriere de l’etat
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de transition de l’isomere E-3B lorsqu’il subit une fermeture electrocyclique de cycle conduisant a la formation de 4B.
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Dans le but de pouvoir mieux evaluer l’effet d’un substituant alkyle sur la reactivite, on a compare la photoreactivite de
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1B a celles de ses analogues, les derives methyle (1A) et isopropyle (1C).
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Mots-cles : groupes protecteurs photolabiles, photoenols, photolyse eclair au laser, deplacement 1,5 d’un atome d’hy-
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drogene, fermeture electrocyclique de cycle, lactonisation intramoleculaire.
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[Traduit par la Redaction]
potential use in such a wide variety of applications,
photoremovable protecting groups with diverse physical
properties are desirable. Furthermore, detailed knowledge of
the photorelease mechanism makes it easier to determine the
best-suited photoremovable protecting groups for each appli-
cation.
We have shown that ester 1C releases its alcohol moiety
upon irradiation, and that the release is independent of the
reaction medium.8,9 The release from 1C is initiated by in-
tramolecular H-atom abstraction by the triplet ketone in 1
to form 1,4-triplet biradical 2C, which intersystem crosses
to E and Z-photoenols 3C. Z-3C is short-lived because it
Introduction
In the past few decades, various systems have been de-
signed for use as photoremovable protecting groups, photo-
triggers, and photocaging groups.1–7 Photoremovable
protecting groups have potential use in a wide variety of ap-
plications, such as drug and gene delivery, release of fra-
grances in household products, and as an aid in multistep
synthesis. Furthermore, photoremovable protecting groups
have been used to release bioactive compounds in living tis-
sue and thus make it possible to study physiological events
such as enzyme activity, muscle contraction by ATP hydrol-
ysis, and ion channel permeability. Because they have
Received 5 June 2010. Accepted 18 August 2010. Published on the NRC Research Press Web site at canjchem.nrc.ca on 25 February
2011.
This article is part of a Special Issue dedicated to Professor J. C. Scaiano.
S. Muthukrishnan, Q. Li, B. Seok, G. de Jong, and A.D. Gudmundsdottir.1 Department of Chemistry, University of Cincinnati,
Cincinnati, Ohio 45221, USA.
T.C.S. Pace and C. Bohne. Department of Chemistry, University of Victoria, Victoria, BC V8W 3V6, Canada.
1Corresponding author (e-mail: annag@uc.edu).
Can. J. Chem. 89: 331–338 (2011)
doi:10.1139/V10-161
Published by NRC Research Press

332
Can. J. Chem. Vol. 89, 2011
Scheme 1. Proposed reaction mechanism for photorelease from 1.
ically, about 2 mL of the solutions was placed in 7 mm Â
7 mm Suprasil quartz cells capped with prewashed septa.
These solutions were purged with nitrogen or argon for
10 min. The lifetimes of E-3C were measured as described
earlier.13
Preparation of 1B
To a stirred solution of phthalic anhydride (2.29 g,
15 mmol) in a 1:1 anhydrous diethyl ether – toluene mixture
was added 2-ethylphenyl magnesium bromide, prepared
from 2-bromoethylbenzene (3.0 g, 16 mmol) and magne-
sium turnings (500 mg, 17.8 mmol) in anhydrous diethyl
ether.14 The resulting mixture was refluxed for 12 h and
poured onto ice – hydrochloric acid, and the resulting mix-
ture was extracted with diethyl ether (3 Â 30 mL). The mix-
ture was washed with a 10% NaHCO3 solution, and the
aqueous phase was acidified with 10% aq HCl and extracted
with diethyl ether (3 Â 30 mL). The organic layer was dried
over anhydrous magnesium sulfate and evaporated under
vacuum to yield 2-(2’-ethylbenzoyl)benzoic acid (2.2 g,
8.5 mmol, 56%). Without further purification, the material
was dissolved in methanol, concd H2SO4 (5 mL) was added,
and the mixture was refluxed overnight (16 h). The resulting
mixture was cooled to room temperature, neutralized with
aq NaHCO3, and extracted with diethyl ether (3 Â 40 mL).
The organic layer was dried over anhydrous magnesium sul-
fate and evaporated under vacuum to yield a yellow residue.
The residue was purified by silica gel column chromatogra-
phy to yield methyl 2-(2’-ethylbenzoyl)benzoic acid ester 1B
as a pale yellow oil (2.2 g, 8.2 mmol, 51% yield).
decays by a 1,5-H shift to regenerate 1C. The longer lived
E-3C undergoes electrocyclic ring closure and intramolecular
lactonization to release the alcohol moiety. In comparison,
1A, which has an ortho-methyl group, fails to release its al-
cohol moiety upon irradiation (Scheme 1), even though tran-
sient spectroscopy shows that the major reactivity of 1A
involves intramolecular H-atom abstraction to form Z-3A
and E-3A.10 It was concluded that the short lifetime of
E-3A prevented it from undergoing intramolecular lactoni-
zation and releasing its alcohol.
1
1B: IR (neat, cm–1): 2954, 1725, 1670, 1287, 929, 768. H
In this paper, we compare the photoreactivities of methyl,
ethyl, and isopropyl benzoyl benzoic esters 1A, 1B, and 1C,
respectively, in argon- or nitrogen-saturated solutions by
performing product studies, transient absorption spectro-
scopy, and theoretical calculations. The lifetimes of Z-3 and
E-3 are affected by intramolecular hydrogen bonding, the
steric demand, and the stereoelectronic properties of the
ortho-alkyl groups. The yields of photorelease from 1A, 1B,
and 1C depend on the yields of E-3A, 3B, and 3C and,
more importantly, on their lifetimes.
NMR (400 MHz, CDCl3, ppm) d: 7.92 (m, 1H), 7.38–7.62
(m, 5H), 7.13–7.24 (m, 2H), 3.64 (s, 3H), 3.05 (q, J =
8 Hz, 2H) 1.34 (t, J = 8 Hz, 3H). 13C NMR (100 MHz,
CDCl3, ppm) d: 198.4, 167.3, 145.8, 142.2, 136.4, 131.9,
131.7, 131.4, 130.4, 130.2, 130.1, 129.7, 128.8, 126.8, 52.6,
27.0, 15.7. HRMS (ESI-MS) m/z calcd for C17H16O3Na
[M + Na]+: 291.0997; found: 291.0983.
Photolysis of 1B in argon-saturated 2-propanol
Ester 1B (71 mg, 0.27 mmol) was placed in a Pyrex tube
and dissolved in 2-propanol (7 mL), and the resulting solu-
tion was purged with argon at room temperature for 15 min
and sealed with a rubber septum. The solution was irradiated
using a 450 W medium pressure mercury arc lamp im-
mersed in a Pyrex well for 28 h at room temperature. The
reaction was monitored through thin layer chromatography
(10% ethyl acetate in hexane). After the majority of the
starting material disappeared, the solvent was removed
under vacuum, and the yellow residue was purified with a
silica gel column using a 7:93 ethyl acetate – hexane mixture
to yield 4B as a yellow liquid (35 mg, 15 mmol, 56% yield)
and recovered starting material (25 mg, 0.09 mmol, 35% re-
covery).
Experiments
Laser flash photolysis
Laser flash apparatus
Laser flash photolysis studies were performed using Exci-
mer11 or YAG lasers.12,13 Rate constants were determined by
fitting an average of three to eight kinetic traces. Transient
absorption spectra were obtained by plotting average absorb-
ance values collected from decays at 10 or 20 nm intervals
between 300 and 600 nm.
Sample preparation for laser flash photolysis
4B: IR (neat, cm–1): 2924, 1771, 1465, 934. 1H NMR
(400 MHz, CDCl3, ppm) d: 7.03–7.17 (m, 2H), 7.31–7.64
(m, 5H), 7.98–8.00 (m, 1H), 4.31 (q, J = 8 Hz, 1H), 1.28
(d, J = 8 Hz, 3H). 13C NMR (100 MHz, CDCl3, ppm) d:
169.8, 146.9, 141.9, 133.5, 131.1, 129.4, 128.7, 126.7,
125.6, 123.4, 123.4, 122.4, 90.3, 50.9, 14.7. HRMS (ESI-
Stock solutions of 1A, 1B, and 1C in methanol and aceto-
nitrile were prepared with spectroscopic grade solvents, such
that the solutions had absorptions between 0.6 and 0.8 at
266 nm. Stock solutions of 1A, 1B, and 1C in spectroscopic
grade benzene and acetonitrile were prepared so that the sol-
utions had absorptions between 0.8 and 0.6 at 308 nm. Typ-
Published by NRC Research Press

Muthukrishnan et al.
333
Fig. 1. Photolysis of 1B in CHCl3, C6H6, 2-propanol, and toluene.
Scheme 2. Photolysis of 1A, 1B, and 1C in argon-saturated ben-
zene.
Scheme 3. Photolysis of 1A in argon-saturated methanol.
MS) m/z calcd for C17H16O2 [M + 1]: 237.0916; found:
237.0904.
Quantum yields
Table 1. Quantum yields for depletion of 1 and for-
mation of 4.
Quantum yields for the photolysis of 1B were determined
both for depletion of the starting material and for formation
of product 4B. 2-Propanol was dried over molecular sieves
and distilled prior to use. The mole to area ratio response of
the GC traces was calibrated for compounds 1B and 4B and
valerophenone in 2-propanol, which was the actinometer.15
Irradiation of 0.1 mol/L argon- and nitrogen-saturated 2-
propanol solutions of 1B on a merry-go-round apparatus
using a 450 W medium pressure mercury arc lamp and po-
tassium chromate filter to isolate the 313 nm line was per-
formed to about 10% conversion. At least three replicates
of each sample were irradiated and analyzed with a GC
equipped with an FID detector. The results from all three
replicates were averaged.
Quantum yield for depletion Quantum yield for
of 1
1Aa
1B
formation of 4
0.030 0.003
0.09 0.01
0.17 0.01
4A
4B
4C
0
0.07 0.01
0.14 0.01
1Cb
aSee ref. 10.
bSee ref. 8.
ble yields, indicating that the photorelease is not strongly af-
fected by the solvent (Fig. 1). In contrast, we have reported
that photolysis of 1A yields no products in solvents such as
benzene and chloroform, which do not have easily abstract-
able H atoms. However, in solvents with abstractable H
atoms, 1A yields 5 (Scheme 3), presumably from intermo-
lecular H-atom abstraction from the solvent.10
Theoretical calculations
Density functional theory (DFT) calculations were per-
formed using Gaussian03 at the B3LYP level of theory and
with the 6–31+G(d) basis set.16,17 All transition states were
confirmed to have one imaginary vibrational frequency by
the analytical determination of the second derivative of the
energy with respect to the internal coordinates. Intrinsic re-
action coordinate18 calculations were used to verify that the
transition states corresponded to the correct reactant and
products.19,20 Vertical UV absorption spectra were calculated
using time-dependent density functional theory (TD-
DFT).21–25 The effect of solvation was calculated using the
self-consistent reaction field (SCRF) method with the inte-
gral equation formalism polarization continuum model
(IEFPCM) with methanol and acetonitrile as the sol-
vents.26–30
Quantum yields
The quantum yields for the depletion of 1B and the for-
mation of 4B in 2-propanol are listed in Table 1. The quan-
tum yields for 1C, which have been published previously,
are slightly higher than those for 1B and are listed in Table 1
for comparison.
Calculations
To better understand why 1A, 1B, and 1C react differ-
ently, we calculated the stationary points on their energy
surfaces. We optimized the gas-phase structures of 1A, 1B,
and 1C and their respective first triplet excited states of the
ketone. The C=O bond in the TK of 1 is elongated to
Results and discussion
˚
˚
1.311 A compared with 1.225 A in the S0. The progression
of the C–O bond stretch fits well with the TK of 1 having an
(n,p*) configuration.31–34 The calculated energies of the TKs
of 1A, 1B, and 1C are ~8 kcal/mol (1 cal = 4.184 J) lower
than the measured value for the analogous benzophenone.
However, we have previously shown that DFT calculations
Product studies
Photolysis of 1B in an argon-saturated solution results in
lactone 4B, which is similar to the photoreactivity of 1C
(Scheme 2). Irradiation of 1B in solvents such as benzene,
toluene, chloroform, and 2-propanol yields 4B in compara-
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334
Can. J. Chem. Vol. 89, 2011
Table 2. Intramolecular hydrogen bonds in Z-3 and
E-3.
Scheme 4. Calculated transition state barriers for E-3, 6, and 7.
Bond vibrational
frequency
Bond length
˚
Compound
Z-3A
O–H (cm–1)
3479
C=O H–O– (A)
1.783
Z-3B
3480
1.782
Z-3C
3459
1.740
E-3A
3506
1.800
E-3B
E-3C
3504
3490
1.7821
1.756
underestimate the energy of triplet ketones with an (n,p*)
configuration.35
We optimized the structures of biradicals 2A, 2B, and 2C
and found that their lowest energy conformers have intramo-
lecular hydrogen bonding between the O–H group and the
C=O ester group. The hydrogen-bonded conformers are ~5–
8 kcal/mol lower in energy than those that do not have intra-
molecular hydrogen bonding. The calculated O–H and C=O
stretches in the hydrogen-bonded conformer of 2A are lo-
cated at 2996 and 1662 cm–1, respectively, but the corre-
sponding stretches are at 3742 and 1768 cm–1 in a
conformer of 2A that does not undergo intramolecular hy-
drogen bonding. Thus, the calculated IR spectra confirm the
intramolecular hydrogen bonding in the lowest energy con-
formers of 2A, 2B, and 2C.
The structures of Z-3 and E-3 with intramolecular hydro-
gen bonding were also optimized. Enols Z-3 and E-3 are be-
tween 35 and 40 kcal/mol higher in energy than
corresponding ketones 1A, 1B, and 1C. Furthermore, Z-3 is
between 1 and 3 kcal/mol more stable than the correspond-
ing E-3 molecule. The intramolecular hydrogen bond in Z-
3C is shorter and has a lower vibrational frequency than
that in Z-3A and Z-3B and is therefore stronger (Table 2).
Similarly, the intramolecular hydrogen bond in E-3C is
found to be stronger than that for E-3A and E-3B.
We calculated the transition state for the TK of 1 for the
H-atom abstraction to form biradical 2. The transition-state bar-
rier for g H-atom abstraction of the TK of 1A is ~8 kcal/mol,
whereas the transition-state barriers for the TKs of 1B and
1C are less by 3 and 4 kcal/mol, respectively. The stationary
points on the energy surfaces of 1A–1C are plotted in Figs.
2–4. These plots highlight that the intramolecular H-atom
abstraction from the TK of 1A, 1B, and 1C to form biradi-
cals 2A, 2B, and 2C can be easily achieved at ambient tem-
perature. Even though biradical 2A is a primary radical, it is
only ~3 kcal/mol less stable than 2B and 2C, presumably
because the radical center on the ortho-methylene is stabi-
lized owing to conjugation with the aromatic rings. The
driving force for the reactivity of E-3 and Z-3 must be the
re-aromatization of the benzene ring.
the ethyl group can, causes the transition-state barrier for the
1,5 H-atom shift in Z-3C to increase to 7.9 kcal/mol.
The calculated transition states for electrocyclic ring clo-
sure of E-3 show that alkyl substituents stabilize this transi-
tion state (Scheme 4). Thus, the transition-state barrier for
E-3A is the highest, and the barriers for E-3B and E-3C are
lower. The steric effect of the dimethyl substituents in E-3C
twists its butadienyl moiety. The torsion angle between the
butadienyl moiety in E-3C is 448, but only 338 and 288 in
E-3B and E-3A, respectively. In the electrocyclic ring clo-
sures, twisting of the butadienyl moiety to a distorted struc-
ture moves the reactant along the potential energy surface
towards the transition state’s twisted geometry. So the steric
effect of the dimethyl substituent in E-3C lowers the transition-
state barrier for forming 6C by twisting the butadienyl moi-
ety.
Furthermore, we calculated the transition-state barrier for
6 to undergo lactonization and found that the barrier for lac-
tonization is ~40 kcal/mol, which is considerably higher
than the transition-state barrier for E-3 to undergo electrocy-
clic ring closure. However, it is complicated to compare
these transition-state barriers because solvation is expected
to affect the lactonization significantly more than the elec-
trocyclic ring closure. The calculated transition-state barriers
make it possible to evaluate the effect of the alkyl substitu-
ents on these two processes rather than to obtain their abso-
lute values. The steric demand of the dimethyl group in 6C
makes the lactonization slightly less feasible than for 6A
and 6B.
We calculated the transition states for Z-3 to reform 1 via
1,5 H-atom shifts (Table 3 and Fig. 5). The transition-state bar-
rier for Z-3A to reform 1A is 7.2 kcal/mol and 6.6 kcal/mol
for Z-3B to form 1B. Presumably, the electron-donating ef-
fect of the ethyl groups stabilizes the transition state more
than the methyl group stabilizes it. In comparison, the steric
demand of the isopropyl group, which cannot rotate away as
We calculated the transition states for lactonization of E-
3A, 3B, and 3C to form 7. The transition-state barrier is
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Muthukrishnan et al.
335
Fig. 2. Calculated stationary points on the energy surface for 1A. The energies are in kcal/mol (1 cal = 4.184 J) and are obtained from the
singlet- (black) and triplet-optimized structures with zero point energy corrections included. Numbers in parentheses are energies calculated
with a polarization continuum model (PCM) model for methanol.
Fig. 3. Calculated stationary points of the energy surface for 1B. The energies are in kcal/mol (1 cal = 4.184 J) and are obtained from the
singlet- (black) and triplet-optimized structures with zero point energy corrections included. Numbers in parentheses are energies calculated
with a polarization continuum model (PCM) model for methanol.
~43 kcal/mol for E-3. The calculations demonstrate that the
ortho-alkyl substituent has minimal effect on the lactoniza-
tion of E-3. In comparison, the calculated transition-state
barrier for 7 to form 4 shows that ring closure of 7A is the
least favored as expected, since its butadienyl moiety is less
twisted than for 7B and 7C.
Thus, the calculations show that the electrocyclic ring clo-
sure of E-3 and 6 are affected by the alkyl substituents,
whereas lactonization of E-3 is not. However, the transition-
state barrier for lactonization of 6C is increased by the steric
demand of the dimethyl group.
to triplet biradical 2B on the basis of its similarity to the
transient spectra of the analogous 1,4-biradical 2A.9,10 The
TD-DFT calculations support this assignment because the
major calculated electronic transition for 2B is located at
336 nm (f = 0.0871) in the gas phase and at 334 nm (f =
0.1104) in methanol. In oxygen-saturated solutions, the ab-
sorption owing to 2B was quenched. As the absorption band
for 2B decayed, a new transient with a lmax at 390 nm
(Fig. 6) formed at the same rate. We assign this absorption
to Z-3B and E-3B, based on comparison with the transient
spectra of 3A and 3C.8,10 The TD-DFT calculations also
support this assignment as they revealed that the major ab-
sorption bands of Z-3B and E-3B are located at 426 nm
(f = 0.1975) and 437 nm (f = 0.0699) in methanol, respec-
Laser flash photolysis of 1B in nitrogen-saturated metha-
nol produced a transient spectrum with a lmax at ~330 nm
with a lifetime of ~53 ns (Fig. 6) We assign this absorption
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336
Can. J. Chem. Vol. 89, 2011
Fig. 4. Calculated stationary points on the energy surface for 1C. The energies are in kcal/mol (1 cal = 4.184 J) and are obtained from the
singlet- (black) and triplet-optimized structures with zero point energy corrections included. Numbers in parentheses are energies calculated
with a polarization continuum model (PCM) model for methanol.
Table 3. Calculated transition-state (TS)
barriers for the 1,5 H-atom shift in Z-3.
Fig. 6. Laser flash photolysis of 1B in N2-saturated methanol over
(A) a time window of 1 ms and (B) a time window of 200 ms.
Compound
Z-3A
Z-3B
TS barrier (kcal/mol)
7.2
6.6
7.9
Z-3C
Note: 1 cal = 4.184 J.
Fig. 5. Transition state for 1,5 H-atom shift in Z-3A, Z-3B, and Z-
3C.
not form hydrogen bonds with the photoenols, are shown in
Fig. 7. The ratios of Z-enol to E-enol were measured from
the absorbance at 390 nm by measuring the combined ab-
sorptions of Z-3 and E-3 on shorter timescales and the ab-
sorption of E-3 on longer timescales. The Z:E ratio was
highest for 3A at 1:1.2 and somewhat lower for 3C (3.2:1)
and 3B (3.5:1). Thus, by assuming that E-3 and Z-3 have
similar absorption coefficients, the quantum yields for enol
formation from 1A is only half that observed for 1B and
1C (Fig. 7). The lower yield of photoenols from 1A is a re-
flection that the intramolecular H-atom abstraction is less fa-
vorable in the TK of 1A than in that of 1B and 1C.
However, the Z:E ratio is the lowest for 3A, presumably be-
cause intramolecular rotation in 2A is less hindered than in
2B and 2C. We have previously shown that restricted intra-
molecular rotation in analogous biradicals results in less E-
photoenol formation.38
tively. The lifetimes of Z-3B and E-3B in methanol are
15 ms and >3 ms, respectively. The lifetimes for each com-
ponent can be obtained by fitting the decay with a monoex-
ponential function because the decay of Z-E3 is complete
before E-3B has decayed significantly (Fig. 7). In acetoni-
trile, the lifetime of Z-3B is reduced to 2.5 ms, and the life-
time of E-3B is >19 ms. This is in agreement with previous
reports that show that the Z-photoenols from o-methyl ben-
zophenone and o-methyl acetophenones are longer lived in
solvents that can form hydrogen bonds with the photoen-
ols.36,37
We have reported the laser flash photolysis of 1A and 1C
previously;8 however, in this paper we compare the lifetimes
and yields of biradicals 2A, 2B, and 2C and photoenols 3A,
3B, and 3C (see Table 4). The lifetimes of biradicals 2A,
2B, and 2C are similar within experimental error, which fits
well with the calculations that predict that these biradicals
have similar stabilities.
The lifetime of Z-3C is the longest in all solvents
(Table 4), whereas that of Z-3B is only somewhat shorter
lived and that of Z-3A is considerably shorter. The lifetime
The ratios of Z-3 and E-3 in benzene (Fig. 7), which can-
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Muthukrishnan et al.
337
Fig. 7. Decay of E-3 and Z-3 at 390 nm in N2-saturated benzene.
The kinetic traces are obtained under identical conditions, thus
showing relative yields for forming Z-3 and E-3.
ring closure followed by lactonization. Our hypothesis is
based on the observation that E-3A does not produce 4A in
nonpolar solvent, whereas E-3A has lifetimes that are simi-
lar as observed for E-3B and that the transition-state barrier
for E-3A to undergo electrocyclic ring closure is larger than
that for E-3B and E-3C. In comparison, the calculated
transition-state barrier for lactonization of E-3 is not af-
fected significantly by the alkyl substituents.
Conclusion
The product studies show that 1B and 1C release their al-
cohol moiety upon irradiation via photoenolization and form
4B and 4C, whereas 1A also undergoes photoenolization,
but both Z-3A and E-3A decay back to the starting material.
Laser flash photolysis shows that 1A, 1B, and 1C all
undergo H-atom abstraction to form 2, which intersystem
crosses to form E-3 and Z-3. The yields of the photoenols
are similar for 1B and 1C and slightly less for 1A in ben-
zene. The calculations further support this because stationary
points on the energy surface of these esters are very similar.
The lifetime of E-3A is significantly shorter in methanol
than that of both E-3B and E3C. Thus, E-3A does not react
to release its alcohol moiety but rather regenerates 1A. In
comparison, the lifetime of E-3A is considerably longer in
benzene and acetonitrile, however, because the electrocyclic
ring closure for E-3A is less favorable than for E-3B, it re-
ketonizes faster than it undergoes electrocyclic ring closure.
Thus, in designing photoprotecting groups based on intramo-
lecular photoenolization, it is important to consider the ef-
fect of the alkyl substituent on electrocyclic ring closure
and lactonization.
Table 4. Measured lifetimes of 2, E-3 and Z-3 in
N2-saturated solutions.
Lifetime
Compound
2A
Z-3A
E-3A
2B
Z-3B
E-3B
2C
Z-3C
E-3C
Benzene
77 ns
0.09 ms
1<t>8 ms
50 ns
~0.7 ms
1<t>8 ms
70 ns
MeCN
57 ns
1.2 ms
10 ms
58 ns
2.5 ms
19 ms
83 ns
8 ms
MeOH
54 ns
6.5 ms
162 ms
33 ns
15 ms
>3 ms
60 ns
17 ms
>0.1 s
Acknowledgement
This work was supported by the Petroleum Research Fund
administrated by the American Chemical Society and the
Ohio Supercomputer Center. Partial funding of this project
was provided by the National Science Foundation (NSF).
M.S. acknowledges the Harry Mark Research Fellowship.
C.B. and T.C.S.P. thank the Natural Sciences and Engineer-
ing Research Council of Canada (NSERC) for funding at the
University of Victoria, Victoria, British Columbia, and
1.2 ms
>500 ms
>0.1 s
of Z-3A in methanol is comparable to the analogous Z-enol
from 2,4-methyl benzophenone,37 whereas the lifetime of Z-3A
in benzene is considerably longer. Wagner and co-workers37
showed that the 1,5 H-atom shifts are retarded by intermolecular
hydrogen bonding. Thus, we theorize that intramolecular hy-
drogen bonding also renders Z-3 more stable towards a 1,5
H-atom shift. The steric factors of the alkyl substituent in Z-
3B and Z-3C also retard the 1,5-hydrogen shift, and thus
they are longer lived than Z-3A.
The lifetime of E-3A was shorter than for E-3B in aceto-
nitrile and methanol, whereas the lifetimes in benzene are
comparable. E-3C is longer lived than both E-3A and E-
3B. Unlike the Z-photoenols, the E-photoenol reketonization
is solvent-assisted. Furthermore, in competition with reketo-
nization, E-3B and E-3C must undergo electrocyclic ring
closure and intramolecular lactonization to form 4B and 4C,
respectively. E-3A reketonizes faster than it undergoes elec-
trocyclic ring closure or lactonization. Thus, we theorize that
in nonpolar solvents, E-3B and E-3C decay by electrocyclic
T.C.S.P. thanks NSERC for
a
Canada Graduate
Scholarships – Doctoral (CGS-D) scholarship. A.D.G. is
grateful for having had the opportunity to spend a sabbatical
in the laboratory of Professor Scaiano.
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