Photochemistry of 2-alkoxymethyl-5-methylphenacyl chloride and benzoate

Article abstract of DOI:10.1021/jo061169j

Irradiation of 2-(alkoxymethyl)-5-methyl-α-chloroacetophenones (1a-c) and 2-(methoxymethyl)-5-methylphenacyl benzoate (1d) in dry, nonnucleophilic solvents afforded 3-alkoxy-6-methylindan-1-ones (3a-c) in very high chemical yields. 3-Methylisobenzofuran-1

Full text of DOI:10.1021/jo061169j

Photochemistry of 2-Alkoxymethyl-5-methylphenacyl Chloride and
Benzoate
Luka´sˇ Pl´ısˇtil,† Toma´sˇ Sˇolomek,† Jakob Wirz,‡ Dominik Heger,‡ and Petr Kla´n*,†
Department of Organic Chemistry, Faculty of Science, Masaryk UniVersity,
Kotlarska 2, CZ-61137 Brno, Czech Republic, and Departement Chemie der UniVersita¨t Basel,
Klingelbergstrasse 80, CH-4056 Basel, Switzerland
klan@sci.muni.cz
ReceiVed June 7, 2006
Irradiation of 2-(alkoxymethyl)-5-methyl-R-chloroacetophenones (1a-c) and 2-(methoxymethyl)-5-
methylphenacyl benzoate (1d) in dry, nonnucleophilic solvents afforded 3-alkoxy-6-methylindan-1-ones
(3a-c) in very high chemical yields. 3-Methylisobenzofuran-1(3H)-one (2) was, however, isolated as a
major photoproduct in the presence of trace amounts of water. Quenching experiments and laser flash
spectroscopy revealed that the indanone derivatives 3 are formed by 1,5-hydrogen migration from the
lowest triplet excited state of the acetophenones 1 and cyclization of the resulting photoenols. In contrast,
production of the lactone 2 in wet solvents was found to result from two consecutive photochemical
transformations. The photoenols produced by photolysis of 1a-c add water as a nucleophile to form
2-acetyl-4-methylbenzaldehyde (4), which is further converted to 2 via a second, singlet state
photoenolization process. Exhaustive photolysis of 1a in methanol produced the acetal 2-(dimethoxym-
ethyl)-5-methylacetophenone (7a) as the exclusive product. The remarkable selectivity of these
photoreactions may well be useful in synthetic organic chemistry.
Introduction
dergoes intramolecular hydrogen abstraction via the triplet state
to form a short-lived triplet enol E, yielding two isomeric
3
The photochemistry of 2-alkylphenyl ketones has been the
subject of numerous studies and the reaction mechanism is now
well-established.1-13 For example, 2-methylacetophenone un-
photoenols, E and Z, while direct enolization from the lowest
excited singlet state produces the Z-isomer only2,14-18 (Scheme
1). The Z isomer, having a lifetime similar to that of the triplet
enol, is converted efficiently back to the starting molecule, but
the E isomer may, in the absence of trapping agents such as
* Corresponding author. Phone: +420-549494856. Fax: +420-549492688.
† Masaryk University.
‡ Universita¨t Basel.
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10.1021/jo061169j CCC: $33.50 © 2006 American Chemical Society
Published on Web 09/21/2006
8050
J. Org. Chem. 2006, 71, 8050-8058

2-Alkoxymethyl-5-methylphenacyl Chloride and Benzoate
SCHEME 1
SCHEME 2
SCHEME 3. Synthesis of 1a-c Using a Photochemical Step
tions to afford trans-3-arylisochromanols.35 A photoenolization-
electrocyclization sequence was applied in the total synthesis
of quinoidic natural product G-2N, a powerful antiretroviral
agent.36 Various functionalized 1-indanones were synthesized
using photoenolization reactions by Wessig and co-workers.37
The 1-indanone skeleton can also be prepared by conventional
procedures, which are based on the pentanone ring closure and
they incorporate intramolecular SN reactions.38-44
dienophiles, persist up to seconds because its reketonization
requires proton transfer through the solvent. Photoenols may
also cyclize to the corresponding cyclobutenols.19
When leaving groups are present in an appropriate position,
the primary photoenols can undergo elimination reactions. Thus,
2-substituted 2-ethylbenzophenones20 or 2-ethylacetophenones21,22
release the substituent efficiently upon irradiation. Similarly,
leaving groups on the R-carbon of 2-methylphenacyl compounds
are efficiently released.23-25 Such chromophores were proposed
as photoremovable protecting groups for various applications
in organic synthesis or biochemistry.7,26,27
This paper reports our mechanistic study of unexpected
phototransformations of 2-alkoxymethyl-5-methylphenacyl chlo-
ride or benzoate.
There are other examples in which photoenolization is utilized
in organic synthesis. A short-lived E photoenol can be, for
example, trapped in a Diels-Alder fashion by electron-deficient
dienophiles.28-31 The total syntheses of the antitumor agent
hybocarpone or cytotoxic hamigerans were recently reported
by Nicolaou and co-workers.32-34 Photoenols generated by
photolysis of 2-tolualdehydes in the solid state react with the
precursor aldehydes in hetero-Diels-Alder cycloaddition reac-
Results and Discussion
Products. Irradiation of 2-(methoxymethyl)-5-methyl-R-
chloroacetophenone (1a) at λ > 280 nm was originally carried
out to synthesize the corresponding indanone derivative 3-meth-
oxy-6-methylindan-1-one (3a) via a photoenolization step and
the following ring closure reaction, analogous to the reaction
observed with similar systems.7,25,37,45 To our surprise, the
lactone 3-methylisobenzofuran-1(3H)-one (2) was formed in
high yield in addition to 3a (Scheme 2). Methanol, methyl
chloride, and a small amount of 2-acetyl-4-methylbenzaldehyde
(4) were produced as side products. The product distribution
was found to depend strongly on the solvent type (hexane,
benzene, acetonitrile, or methanol) and to be extremely sensitive
to moisture. To elucidate the mechanism of this photochemically
initiated transformation, four acetophenone derivatives (1a-d)
were synthesized and their reactions examined by common
photochemical tools, laser flash photolysis (LFP), and quantum
chemical calculations.
(19) Wagner, P. J.; Subrahmanyam, D.; Park, B. S. J. Am. Chem. Soc.
1991, 113, 709-710.
(20) Tseng, S. U. E. F. J. Am. Chem. Soc. 1976, 98, 541-544.
(21) Pelliccioli, A. P.; Wirz, J. Photochem. Photobiol. Sci. 2002, 1, 441-
458.
(22) Atemnkeng, W. N.; Louisiana, L. D.; Yong, P. K.; Vottero, B.;
Banerjee, A. Org. Lett. 2003, 5, 4469-4471.
(23) Bergmark, W. R.; Barnes, C.; Clark, J.; Paparian, S.; Marynowski,
S. J. Org. Chem. 1985, 50, 5612-5615.
(24) Netto-Ferreira, J. C.; Scaiano, J. C. J. Am. Chem. Soc. 1991, 113,
5800-5803.
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Soc. 2001, 123, 7931-7932.
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(27) Literak, J.; Wirz, J.; Klan, P. Photochem. Photobiol. Sci. 2005, 4,
43-46.
2-(Alkoxymethyl)-5-methyl-R-chloroacetophenones (1a-c)
were prepared by photolysis of 2,5-dimethylphenacyl chloride25
in alcohols, yielding the corresponding 2-(alkoxymethyl)-5-
methyl-acetophenones (5a-c) (∼50%), which were chlorinated
using SO2Cl2 in the subsequent step (Scheme 3).
(28) Arnold, B.; Mellows, S.; Sammes, P. G.; Wallace, T. J. Chem. Soc.,
Perkin Trans. 1 1974, 3, 401-409.
(29) Connolly, T.; Durst, T. Tetrahedron 1997, 53, 15959-15982.
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34, 3459-3468.
(31) Quinkert, G.; Stark, H. Angew. Chem., Int. Ed. Engl. 1983, 22, 637-
655.
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R.; Venugopalan, P. J. Org. Chem. 2004, 69, 8459-8466.
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126, 613-627.
J. Org. Chem, Vol. 71, No. 21, 2006 8051

Pl´ısˇtil et al.
SCHEME 4. Photolysis in Nonpolar Solvents
The chemical yields of lactone 2 and indanone 3a in the
photolysis of 1a (c ) 5 × 10-3 M) at >280 nm (polychromatic
light was used in the preparative experiments) or 313 nm
(quantum yield measurements) were found to be highly sensitive
to the water content in all the solvents used. In dry solvents 3a
was formed exclusively, irrespective of the extent of conversion
(Scheme 4a). Exhaustive irradiation provided 3a in almost
quantitative yields and the best results were obtained when HCl,
produced as a side product, was trapped by NaHCO3 to avoid
possible chemical interferences. When benzene was used without
drying (water content ∼0.05%), 2 was identified as the major
product, while 3a was formed in very low yield. The side
products, methyl chloride and methanol, were detected by NMR
as well as by a headspace analysis. Photolysis of 1a in moist
hexane afforded two minor products in addition to 2, namely,
2-acetyl-4-methylbenzaldehyde (4), which was isolated in ∼15%
yield, and 2-hydroxy-2-(methoxymethyl)-5-methylacetophenone
(6a) in trace amounts (Scheme 4b). The lactone 2 was eventually
isolated as the sole product formed after exhaustive irradiation.
For analytical comparison, 6a was alternatively prepared in high
yield by methanolysis of 4 at 20 °C (Scheme 4c). Exhaustive
irradiation of 1a in wet acetonitrile (polar, aprotic, and non-
nucleophilic) led to the formation of a nearly equimolar mixture
of the products 2 and 3a. When pure 2-acetyl-4-methylbenzal-
dehyde (4), which had been isolated from the photolysis of 1a,
was irradiated in either hexane or acetonitrile solution, 3-me-
thylisobenzofuran-1(3H)-one (2) was isolated in near quantita-
tive yield (Scheme 4d).
Irradiation of 1a in wet or dry CD3OD to low conversions
led to isotopic exchange at the 2-methylene position (d-1a),
while exhaustive photolysis produced an acetal, 2-(dimethoxy-
methyl)-5-methylacetophenone (d-7a), as the exclusive product
(Scheme 5). Compound 7a was also photochemically synthe-
sized from 1a, to hydrolyze it to 4, which was needed in our
mechanistic studies and for analytical purposes. These results
clearly indicated that the starting material undergoes a photo-
(40) Pletnev, A. A.; Larock, R. C. Tetrahedron Lett. 2002, 43, 2133-
2136.
SCHEME 5
(41) Brunette, S. R.; Lipton, M. A. J. Org. Chem. 2000, 65, 5114-5119.
(42) Ghosal, M.; Karpha, T. K.; Pal, S. K.; Mukherjee, D. Tetrahedron
Lett. 1995, 36, 2527-2528.
(43) Keumi, T.; Matsuura, K.; Nakayama, N.; Tsubota, T.; Morita, T.;
Takahashi, I.; Kitajima, H. Tetrahedron 1993, 49, 537-556.
(44) Nikolaev, V. A.; Popik, V. V. Tetrahedron Lett. 1992, 33, 4483-
4486.
(45) Bergmark, W. R. J. Chem. Soc., Chem. Commun. 1978, 61-62.
8052 J. Org. Chem., Vol. 71, No. 21, 2006

2-Alkoxymethyl-5-methylphenacyl Chloride and Benzoate
TABLE 1. Photochemistry of 2-Alkoxy-5-methylphenacyl Derivatives 1a-da
starting
material
water
d
e
solvent
hexane
hexane
benzene
benzene
acetonitrile
acetonitrile
contentb
% yield (2)c
Φ1f2
% yield (3)c
Φ1f3
1a
dry
wet
dry
wet
dry
wet
0
95
0
88
0
n.d.
98
3
0.022 ( 0.001
0.007 ( 0.001
0.08 ( 0.01
0.022 ( 0.001
0.26 ( 0.01g
0.16 ( 0.04g
0.23 ( 0.01f
n.d.
0.16 ( 0.01
95g
10
98
62
n.d.
36
0.09 ( 0.01
1b
1c
1d
acetonitrile
acetonitrile
dry
wet
0
21
n.d.
0.06 ( 0.01
98
76
0.28 ( 0.01
0.22 ( 0.02
acetonitrile
acetonitrile
dry
wet
0
18
n.d.
0.014 ( 0.008
98
80
0.29 ( 0.02
0.26 ( 0.02
0.050 ( 0.002g
0.031 ( 0.001g
0.071 ( 0.006g
0.056 ( 0.009g
hexane
hexane
acetonitrile
acetonitrile
dry
wet
dry
wet
0
60
0
n.d.
0.050 ( 0.002
n.d.
98
35
98
69
29
0.008 ( 0.002
a The starting material concentration was 3-5 × 10-3 M; the samples degassed by purging with Ar; n.d. ) not detected. b The water concentration in wet
solvents was 5-50 × 10-3 M. c Exhaustive Pyrex-filtered irradiation (>280 nm) in the presence of NaHCO3 (GC). d The quantum yield of 2 formation at
313 nm (the conversions were kept below 10%). e The quantum yield of 3 formation at 313 nm (the conversions were kept below 10%). f The combined
quantum yield for formation of 4 (almost the exclusive product at low conversions) and 2; 6a was formed in trace amounts. g 5a was formed in trace
amounts.
TABLE 2. Photochemistry of 4a
and 4d). The quantum yields were low in both solvents and
solvent
water contentb
Φ4f2
hardly affected by water addition. The quantum yield Φ4f2 is
comparable to Φ1af2 in wet acetonitrile, but it is almost an order
of magnitude lower than Φ1af2 in wet hexane. This will be
discussed below; we emphasize here that Φ1f2 (Table 1)
obtained in this solvent is the combined quantum yield for the
formation of 2 and 4. The latter was completely consumed upon
exhaustive irradiation, which led to a 98% chemical yield of 2.
hexane
hexane
acetonitrile
acetonitrile
dry
wet
dry
wet
0.032 ( 0.006
0.030 ( 0.002
0.068 ( 0.003
0.061 ( 0.002
a The starting material concentration was 3 × 10-3 M. The samples were
degassed by purging with Ar and irradiated at 313 nm. b The water
concentration in wet solvents was 5-50 × 10-3 M.
An indanone moiety is known to be produced by photoeno-
lization of similar substituted phenyl ketones containing good
(halide, sulfate)24,25,45,47 or even poorer (carboxylate, carbon-
ate)7,26,27 leaving groups in the R-position. Wessig and co-
workers have utilized this reaction for the synthesis of 2,3-
disubstituted indanones from the corresponding substituted
2-methyl and R-methylacetophenones.37 We were initially
interested in the synthesis of 3-alkoxyindanones, but the
electron-donating substituent on the ortho methyl group of the
phenacyl chloride 1a significantly altered the anticipated
behavior. Our first findings indicated that at least two different
photochemical processes occurred when 1a was photolyzed.
While indanone 3a was apparently formed directly from 1a,
the lactone 2 was unquestionably produced by photochemical
transformation of 4, a primary product isolated from photolysis
of 1a. Production of methyl chloride (Scheme 4b), in addition
to methanol, was suggested to be a secondary substitution
process, which is enabled by HCl release in the first photo-
chemical step, especially at higher reaction conversions. This
assumption was easily verified by equilibrating the solution of
methanol and HCl under identical reaction conditions.
enolization process2,46 and that the presence of nucleophilic
methanol prevents the reactions observed in non-nucleophilic
solvents.
Chemical and Quantum Yields. Table 1 documents the
exceptional reaction selectivity of the photoinduced transforma-
tions of R-chloroacetophenones 1a-c and of R-benzoyloxyac-
etophenone 1d, which are observed in dry and wet non-
nucleophilic solvents. Although indanone 3a was the sole
product formed by irradiation of 1a in dry nonpolar solvents,
the quantum yields Φ1af3a were relatively low. Addition of
water suppressed these values further, while formation of lactone
2 (Φ1af2) represented the main photodegradation pathway. In
contrast, Φ1af3a was found to be high in dry acetonitrile and
comparable to Φ1af2 in wet acetonitrile. The ratio of the product
concentrations, [2]:[3], was found to be practically independent
of the water concentration when more than equimolar water
amounts were used. The replacement of a good leaving group
(chloride in 1a) by a poorer one (benzoate in 1d) caused a
considerable quantum efficiency decrease of indanone cycliza-
tion in acetonitrile and of lactone formation in both hexane and
acetonitrile; nevertheless, exhaustive irradiation provided high
chemical yields of both major products in wet solvents. The
larger ethoxy and n-butoxy groups in 1b and 1c, respectively,
somewhat affected both Φ1f2 and Φ1f3; lactone formation was
slightly reduced with increasing size of the alkoxy substituent.
Table 2 lists the quantum yields of the production of lactone
2 by irradiation of 2-acetyl-4-methylbenzaldehyde 4, the
intermediate trapped during the photolysis of 1a (Schemes 4b
The excited state responsible for the reaction of 1a was
identified by facile quenching of product formation with a
typical triplet quencher (piperylene). The formation of 3a from
1a in dry hexane or acetonitrile was prevented by addition of 3
M piperylene, while the production of 2 was quenched only in
wet acetonitrile but not in wet hexane. Besides, piperylene
addition had no effect on the formation of 2 from 4 in any of
the solvents used. This indicates that the formation of indanone
3a and of acetylbenzaldehyde 4 in acetonitrile is initiated from
(46) Michalak, J.; Wolszczak, M.; Gebicki, J. J. Phys. Org. Chem. 1993,
6, 465-470.
(47) Klan, P.; Pelliccioli, A. P.; Pospisil, T.; Wirz, J. Photochem.
Photobiol. Sci. 2002, 1, 920-923.
J. Org. Chem, Vol. 71, No. 21, 2006 8053

Pl´ısˇtil et al.
ylcyclohexa-2,4-dienylidene)ethanol; E-8a; Scheme 6). The
latter is formed only by the triplet pathway, i.e., via the triplet
3
state of the ketone and of the enol, E; it is suppressed in the
presence of 2 M piperylene. The yield of Z-8a was generally
much higher than that of E-8a. Z-Photoenols undergo fast
reketonization and their lifetimes are usually on the order of
hundreds of nanoseconds in nonpolar solvents.2,7,14,25 The
observed microsecond lifetimes (Table 3) indicate that Z-8a is
stabilized by an intramolecular hydrogen bond, particularly in
nonpolar solvents, and/or by resonance stabilization from an
adjacent methoxy group.
LFP of 1a in acetonitrile also caused the rapid formation of
a short-lived transient with λmax ) 340 nm. The lifetime of this
transient, τ ≈ 2.2 µs, was reduced to about 250 ns in aerated
solution and it was assigned to the triplet enol, 3E (Scheme 6),
in accord with the literature.7,25 The lifetime of 3E is somewhat
longer than usual, which may be attributed to biradical stabiliza-
tion by the electron-donating methoxy group.
FIGURE 1. Transient absorption spectrum of 1a in degassed aceto-
nitrile at a delay of 20 ns after the flash. The inset shows a kinetic
trace recorded at 390 nm. The long-lived end absorption decays to
baseline on the ms time scale.
TABLE 3. Lifetimes τ of Transient Intermediates Formed by LFP
(248 or 308 nm) of 1aa
Assignment of the major components to the Z- and E-enols
of 8a does not identify the configuration of the double bond
bearing the methoxy group ((6Z) or (6E); Figure 2). Presumably,
both isomers are formed in comparable yields and they have
slightly different lifetimes: In several cases, the enol decay
traces recorded at 400 nm did not fit a first-order rate law
accurately (footnotes of Table 3). Ab initio DFT calculations
employing B3LYP/6-31+G** were carried out to determine the
relative energies of the photoenol isomers and to evaluate the
stabilization of Z-8a by hydrogen bonding (Figure 2). The -O-
H‚‚‚O(CH3) distance was found to be 1.651 Å in the (6Z)-isomer
of Z-8a. The angle between those two substituents was
calculated to be 159.3°, which is close to a linear geometry
typical for strong hydrogen bonds. No such intramolecular
arrangement is achievable in the (6E)-Z-8a (1). The hydrogen
atom in this isomer is not coplanar with the double bond system.
The calculations validated attribution of the observed longer
lifetimes of Z-8a (Table 3) to hydrogen bonding. The calcula-
tions also showed that the energy of the (6E)-isomer of E-8a is
higher than that of the (6Z)-isomer by 4.1 kcal mol-1 (not
shown), which may be explained by a steric hindrance of the
methylene group hydrogens and the hydrogen atom of the
double bond.
τ(Z-8a)/µs,
τ(E-8a)/ms,
solvent
λobs ) 400 nm
λobs ) 400 nm
hexaneb
ca. 20c
0.29 ( 0.03
0.16 ( 0.04
ca. 7d
very weak
0.35 ( 0.05
0.15 ( 0.01
ca. 300e
acetonitrile dry (<0.05% of water)
acetonitrile wet (2.5% of water)
benzene dry (molecular sieve)
benzene (water-saturated)
0.9 ( 0.1
80 ( 10
a Air-saturated solutions. The yields and lifetimes of the enol transients
were not significantly affected by degassing. b Water saturation had no
substantial effect. cNot accurately first-order; fitting of a biexponential rate
law gave lifetimes of ca. 10 and 50 µs. d Not accurately first-order; fitting
of a biexponential rate law gave lifetimes of ca. 5 and 10 µs. e Not accurately
first-order; a minor component decayed with a lifetime of about 50 ms.
the triplet state, whereas 4, and consequently 2, are produced
via a singlet pathway in hexane.
2-Alkylphenyl ketones are known to have π,π* lowest triplet
states.48 Nevertheless, photoenolization from the triplet state is
an efficient process,25 presumably because the π,π* and n,π*
triplet states are nearly degenerate.49 Formation of the interme-
diates 6a and 4, which were isolated at lower conversions, an
isotopic exchange signifying the photoenolization step, and
observation of the phototransformation 4 f 2 were the most
important initial pieces of evidence required to interpret the
following time-resolved study.
Laser Flash Photolysis. LFP of 1a in hexane and acetonitrile
at 248 nm, or in benzene at 308 nm, gave broad transient
absorptions, λmax ≈ 400 nm (Figure 1), which are assigned to
the photoenol intermediates 8a. The decay of the photoenols
usually obeyed biexponential kinetics (Table 3, Figure 1). The
amplitudes and the decays of these transients were not signifi-
cantly affected by the presence of oxygen, but depended strongly
on the solvent and on the presence of water. By analogy to the
results obtained with parent 2-methylphenacyl chloride and with
use of the arguments given there,25 we assign the major
components of the decay traces to the photoenols with Z-
configuration of the enol function ((1Z)-2-chloro-1-(-6-(meth-
oxymethylene)-3-methylcyclohexa-2,4-dienylidene)ethanol; Z-8a;
Scheme 6). The minor components are attributed to the
E-photoenol ((1E)-2-chloro-1-(-6-(methoxymethylene)-3-meth-
Formation of 6a, which could be isolated in trace amounts
from a hexane solution, is a logical intermediate to obtain 4.
Moreover, the observed increase in the quantum yield Φ1f3
that occurs at the expense of Φ1f2 when the alkoxy group in
1a-c becomes larger suggests an increasing steric influence
on the nucleophilic attack of water to the double bond of the
photoenol.
The following study was done to determine whether 2 is
produced exclusively by secondary photolysis of 2-acetyl-4-
methylbenzaldehyde (4), an isolated intermediate obtained from
1a. For the kinetic studies discussed above, solutions were
exposed only to a single laser flash. New transients appeared
upon re-excitation of the solutions with a second laser pulse,
and these new contributions were the same as those obtained
by LFP of 4. Two transients, with λmax ∼ 400 and 370 nm,
were detected (Table 4). While the lifetimes and amplitudes of
the former (major) species were independent of the presence
of oxygen in both hexane and acetonitrile, both were diminished
significantly in the latter (minor) contribution. The photochem-
istry of o-dicarbonyl compounds has been investigated previ-
ously.3,50,51 For example, that of 2-phthalaldehyde was reported
(48) Wagner, P. J.; Klan, P. In CRC Handbook of Organic Photochem-
istry and Photobiology, 2nd ed.; Horspool, W. M., Lenci, F., Eds.; CRC
Press: Boca Raton, FL, 2003; pp 1-31.
(49) Srivastava, S.; Yourd, E.; Toscano, J. P. J. Am. Chem. Soc. 1998,
120, 6173-6174.
8054 J. Org. Chem., Vol. 71, No. 21, 2006

2-Alkoxymethyl-5-methylphenacyl Chloride and Benzoate
SCHEME 6. Photochemistry of 1a in Wet Hexane or Acetonitrile (Blue: Isolated Compounds; Red: Transients Detected;
Black: Anticipated Species)
to yield phthalide as a major product.52,53 For 2-benzoylben-
zaldehyde in benzene or acetonitrile intramolecular hydrogen
transfer leads to the formation of two ketene-enols: E (τ ) 1
ms), showing absorption at 340 and 400 nm, and Z (τ ) 1.5
µs) with λmax ∼ 360 and 430 nm.50 By analogy, we assign the
transient with λmax ) 400 nm to Z-9 and that with λmax ) 370
nm to E-9 (Table 4; Scheme 6). The lifetime of E-9 is reduced
in aerated solutions, which may indicate oxidation by O2, as
observed in the study on 2-phthalaldehyde.3 This intermediate
probably regenerates the starting material 4 by nucleophilic
addition of water. On the other hand, Z-9 must be the precursor
of 2 because the lactone is formed by a singlet pathway, which
gives the Z-enol exclusively. The efficiency of this reaction was,
of course, lowered by a back hydrogen transfer to regenerate
the starting material (4). As shown above (Tables 1 and 2), the
quantum yield Φ1af2 is comparable to Φ4f2 in wet acetonitrile,
but is an order of magnitude higher in wet hexane. The quantum
inefficiency in hexane could be explained by a fast re-
ketonization and/or by a formation of nonproductive E-9, which
decays via nucleophilic addition of water (Scheme 6). The rate
constant for quenching of the E-ketene-enol (from 2-benzoyl-
(50) Netto-Ferreira, J. C.; Scaiano, J. C. Can. J. Chem.-ReV. Can. Chim.
1993, 71, 1209-1215.
(51) Gebicki, J.; Kuberski, S. J. Chem. Soc., Chem. Commun. 1988,
1364-1365.
(52) Schonberg, A. J. Am. Chem. Soc. 1955, 77, 5755.
(53) Kagan, J. Tetrahedron Lett. 1966, 6097.
J. Org. Chem, Vol. 71, No. 21, 2006 8055

Pl´ısˇtil et al.
FIGURE 2. 3D representation and relative standard Gibbs free energies at 298.15 K of the fully optimized B3LYP/6-31+G** local minima of the
ground-state enol Z-8a (without the 5-methyl group). The numbers (1) and (2) designate opposite conformations of the OH group. The relative
population of the conformers in each pair is given in parentheses.
TABLE 4. Lifetimes τ/s of the Transients from 4a
reaction selectivity, controlled by traces of water in the reaction
system, is unquestionably a very intriguing result, which could
be utilized in organic synthesis.
conditions
Z-9 (λmax ) 400 nm)b
E-9 (λmax ) 370 nm)c
degassed hexane
aerated hexane
degassed acetonitrile
aerated acetonitrile
(2.1 ( 0.1) × 10-5
(2.0 ( 0.1) × 10-5
(2.0 ( 0.2) × 10-6
(1.96 ( 0.05) × 10-6
(5.8 ( 0.1) × 10-2
(5.7 ( 0.1) × 10-4
(1.7 ( 0.3) × 10-3
(7.3 ( 0.3) × 10-4
Experimental Section
a Lifetimes measured by LFP (248 nm pulse; 280 nm filter). b Major
transient; the yields were not affected by oxygen. c The transient yields
diminished in the presence of O2 by ∼35% in MeCN and 25% in hexane.
Materials and Methods. NMR spectra were recorded on a 300
MHz spectrometer; 1H and 13C NMR data were measured in CDCl3
with tetramethylsilane as an internal standard. Gas chromatography
was performed on a gas chromatograph equipped with a 15-m
column (5% diphenyldimethylsiloxane). Mass spectra were recorded
on a spectrometer in positive mode with EI. UV spectra were
obtained with matched 1.0-cm quartz cells. All solvents were
purified by distillation before use. Hexane and benzene were dried
over sodium wire; acetonitrile was dried over CaCl2. 2,5-Dimeth-
ylphenacyl chloride was prepared as described.45
Quantum Yield Measurements. The quantum yield measure-
ments were accomplished on an optical bench consisting of a high-
pressure 350 W Hg lamp, a 1/8 m monochromator with grating 200-
1600 nm set to 313 nm, and a 1 cm quartz cell containing the sample
solution (degassed by purging with argon). The light intensity was
monitored by a Si photodiode detector (UV enhanced) with a
multifunction optical power meter. The concentration of all solutions
was adjusted to approximately ∼5 × 10-3 M, if not stated
otherwise. A solution of valerophenone in hexane was used as an
actinometer (Φ ) 0.30 for acetophenone formation).54 The irradi-
ated samples were analyzed using gas chromatography and hexa-
decane was used as an internal standard. The reaction conversions
benzaldehyde) by water has been found by Netto-Ferreira and
Scaiano to be 1.1 × 103 M-1 s-1 in acetonitrile.50
In conclusion, Scheme 6 shows a complete mechanistic
proposal of the photochemical transformation of 1a into the
major products 3a and 2. It includes short-lived transients
detected by LFP, productive or nonproductive isolated as well
as hypothetical intermediates, and byproducts, such as methanol,
methyl chloride, or the acetophenone derivative 5a that is
produced in traces, apparently by homolytic C-Cl bond
cleavage. The production of the major products was found to
be very sensitive to the water content and the polarity of the
solvents. By analogy to previous work,23-25,37 we expected
cyclization to indanone to take place from the triplet excited
ketone. The surprising lactone formation was found to be a
consequence of two consecutive photochemical transformations
that occur in the presence of nucleophilic water. The high
8056 J. Org. Chem., Vol. 71, No. 21, 2006

2-Alkoxymethyl-5-methylphenacyl Chloride and Benzoate
were kept below 10% in order to prevent interference from the
photoproducts. Each sample was measured at least five times and
the relative standard deviation is shown in the tables.
Steady-State Quenching Studies. The steady-state quenching
studies were performed on a merry-go-round apparatus that assured
identical irradiation conditions. Samples in Pyrex tubes (13 × 120
mm) were purged with argon for 15 min before irradiation. Three
argon-purged tubes of each sample were irradiated simultaneously
with a medium-pressure 125 W Tesla mercury lamp.
under an argon atmosphere and the mixture was stirred for 30 min
at 20 °C. The reaction was then quenched with aqueous NaHCO3
(20 mL). The layers were separated and the aquatic layer was
extracted with methylene chloride (2× 20 mL). Combined organic
layers were washed with brine (20 mL) and dried over MgSO4,
and the solvent was removed under reduced pressure. The corre-
sponding product was separated by flash column chromatography
(silica gel; hexane/methylene chloride/ethyl acetate, 33:66:1).
2-(Methoxymethyl)-5-methyl-R-chloroacetophenone (1a). Yield,
0.5 g (42%); colorless crystals; mp 41-43 °C (hexane). IR (KBr):
2925, 2821, 1691, 1261, 1106 cm-1. 1H NMR (300 MHz, CDCl3)
(ppm): δ 2.40 (s, 3H), 3.41 (s, 3H), 4.61 (s, 4H), 7.32 (d, J ) 7.6
Hz, 1H), 7.35 (s, 1H), 7.42 (d, J ) 7.6 Hz, 1H). 13C NMR (75.5
MHz) (ppm): δ 21.2, 48.1, 58.8, 72.6, 128.7, 129.0, 133.1, 134.6,
136.6, 137.4, 195.1. MS (EI, 30 eV): m/z ) 212 (M+), 176, 163,
145, 133, 117, 105, 91, 79, 65. Anal. Calcd for C11H13ClO2: C,
62.12; H, 6.16. Found: C, 62.06; H, 6.12.
2-(Ethoxymethyl)-5-methyl-R-chloroacetophenone (1b). Yield,
0.51 g (40%); colorless crystals. 1H NMR (300 MHz, CDCl3)
(ppm): δ 1.24 (t, J ) 7.1 Hz, 3H), 2.39 (s, 3H), 3.55 (q, J ) 7.1
Hz, 2H), 4.64 (s, 2H), 4.68 (s, 2H), 7.33 (d, J ) 8.0 Hz, 1H), 7.35
(s, 1H), 7.46 (d, J ) 8.0 Hz, 1H). 13C NMR (75.5 MHz) (ppm):
δ 15.3, 21.2, 48.4, 66.6, 70.6, 128.7, 128.8, 132.8, 135.0, 136.6,
137.3, 195.4. MS (EI, 30 eV): m/z ) 227 (M+), 191, 176, 163,
145, 133, 117, 105, 91, 79, 65.
Laser Flash Photolysis Measurements (LFP). The sample
solutions were excited at 248 nm using a KrF excimer laser (pulse
energy ∼ 150 mJ, pulse duration ∼ 25 ns) or at 308 nm (XeCl,
150 mJ, 25 ns). A pulsed Xenon arc provided the monitoring beam
(cell path length 4.5 cm, orthogonal to the excitation pulse). The
monitoring light beam leaving the sample cell could be directed
either to a polychromator that was equipped with a gated image
intensifier and a diode array to measure absorbance difference
spectra at selected delay times after excitation, or to a monochro-
mator-photomultiplier unit to monitor the time dependence of the
transient absorption at given wavelengths. The photomultiplier
output was fed to 50 Ω on a digital oscilloscope. The data from
both an OMA and oscilloscope were analyzed by computer.
Solutions were degassed by three freeze-pump-thaw cycles and
sealed under vacuum before the measurements to avoid quenching
of the transients by oxygen. The samples were freshly prepared
from cyclohexane or methanol (not dried) stock solutions and
discarded after each laser shot.
Photochemical Synthesis of 2-Alkoxymethyl-5-methyl-ac-
etophenones (5a-c). 2,5-Dimethylphenacyl chloride (8.5 g; 46.5
mmol) was dissolved in an aliphatic alcohol (MeOH, EtOH, or
n-BuOH) (1.2 L), NaHCO3 (2 g) was added, and the solution was
purged with argon for 15 min. This stirred mixture was irradiated
with a 400 W mercury UV lamp through a Pyrex filter (>280 nm)
for 20 h at room temperature until the conversion was complete
(GC). The excess solvent was removed under reduced pressure and
the residue was extracted with methylene chloride (100 mL) and
washed two times with water (50 mL) and brine (50 mL). The
organic layer was then dried over MgSO4 and CH2Cl2 was removed
in vacuo. The corresponding product, 2-(alkoxymethyl)-5-methy-
lacetophenone, was separated by flash column chromatography
(silica gel; hexane/diethyl ether, 4:1). 6-Methyl-indan-1-one was
isolated as a byproduct.25
2-(n-Butoxymethyl)-5-methyl-R-chloroacetophenone (1c). Yield,
0.57 g (40%); colorless crystals. 1H NMR (300 MHz, CDCl3)
(ppm): δ 0.93 (t, J ) 7.6 Hz), 1.24-1.34 (m, 2H), 1.55-1.65 (m,
2H), 2.39 (s, 3H), 3.49 (t, J ) 6.6 Hz, 2H), 4.64 (s, 2H), 4.67 (s,
2H), 7.32 (d, J ) 8.1 Hz, 1H), 7.36 (s, 1H), 7.47 (d, J ) 8.1 Hz,
1H). 13C NMR (75.5 MHz) (ppm): δ 14.1, 19.6, 21.2, 31.9, 48.3,
70.8, 71.2, 128.8, 132.9, 134.9, 136.9, 137.3, 195.3. MS (EI, 30
eV): m/z ) 255 (M+), 219, 204, 190, 176, 163, 145, 133, 117,
105, 91, 79, 65.
Preparative Irradiation of 2-(Alkoxymethyl)-5-methyl-R-
chloroacetophenones. The stirred solution of 2-(alkoxymethyl)-
5-methyl-R-chloroacetophenone (1a-c) (2.4 mmol) in acetonitrile
(200 mL) was purged with argon for 15 min and irradiated with a
400 W mercury UV lamp through a Pyrex filter (>280 nm) for 12
h until the conversion was complete (GC). NaHCO3 (1 g) was then
added and the solvent removed under reduced pressure. The residue
was extracted with methylene chloride (50 mL) and washed twice
with water (50 mL) and once with brine (50 mL). The organic layer
was dried over MgSO4 and CH2Cl2 was removed in vacuo. The
products (3-methylisobenzofuran-1(3H)-one (2) and 3-alkoxy-6-
methylindan-1-ones (3a-c)) were separated by flash column
chromatography (silica gel; hexane/methylene chloride/ethyl acetate,
33:66:1). A trace amount of 2-hydroxy-2-(methoxymethyl)-5-
methylacetophenone (6a) was identified by GC-MS ((EI, 30 eV):
m/z ) 193 (M+), 177, 161, 145, 133, 115, 105, 91, 77, 65).
3-Methylisobenzofuran-1(3H)-one (2). Yield, 45%; colorless
crystals; mp 104-105.5 °C (hexane). IR (KBr): 2987, 2929, 1745,
1614, 1043 cm-1. 1H NMR (300 MHz, CDCl3) (ppm): δ 1.53 (d,
J ) 6.6 Hz, 3H), 2.41 (s, 3H), 5.43 (q, J ) 6.6 Hz, 1H), 7.19 (s,
1H), 7.24 (d, J ) 7.6 Hz, 1H), 7.65 (d, J ) 7.6 Hz, 1H). 13C NMR
(75.5 MHz) (ppm): δ 20.3, 22.0, 77.4, 121.9, 123.1, 125.2, 130.1,
145.3, 151.8, 170.4. MS (EI, 70 eV): m/z ) 162 (M+), 147, 119,
91, 77, 65, 51. Anal. Calcd for C10H10O2: C, 74.06; H, 6.21.
Found: C, 73.92; H, 6.22.
2-(Methoxymethyl)-5-methylacetophenone (5a). 5a was syn-
thesized from MeOH. Yield, 4.64 g (56%). The analytical data were
published in our preceding article.7
2-(Ethoxymethyl)-5-methyl-acetophenone (5b). 5b was syn-
1
thesized from EtOH. Yield, 2.2 g (25%); colorless oil. H NMR
(300 MHz, CDCl3) (ppm): δ 1,25 (t, J ) 7.1 Hz, 3H), 2.39 (s,
3H), 2.57 (s, 3H), 3.57 (q, J ) 7.1 Hz, 2H), 4.74 (s, 2H), 7.29 (d,
J ) 7.6 Hz, 1H), 7.49 (s, 1H), 7.53 (d, J ) 7.6 Hz, 1H). 13C NMR
(75.5 MHz) (ppm): δ 15.4, 21.2, 29.4, 66.4, 70.7, 128.2, 129.8,
132.5, 136.7, 137.0, 137.1, 202.0. MS (EI, 70 eV): m/z ) 192
(M+), 177, 163, 147, 117, 91.
2-(n-Butoxymethyl)-5-methyl-acetophenone (5c). 5c was syn-
thesized from n-BuOH. Yield, 1.9 g (19%); colorless oil. 1H NMR
(300 MHz, CDCl3) (ppm): δ 0.93 (t, J ) 7.6 Hz, 3H), 1.35-1.45
(m, 2H), 1.55-1.65 (m, 2H), 2.39 (s, 3H), 2.57 (s, 3H), 3.51 (t, J
) 7.0 Hz, 2H), 4.74 (s, 2H), 7.28 (d, J ) 7.6 Hz, 1H), 7.50 (s,
1H), 7.53 (d, J ) 7.6 Hz, 1H). 13C NMR (75.5 MHz) (ppm): δ
14.1 (broad), 19.6, 21.1, 29.3, 32.0, 70.9, 128.1, 129.9, 132.5, 136.6,
136.8, 136.9, 201.9. MS (EI, 70 eV): m/z ) 220 (M+), 205, 191,
177, 163, 147, 117, 91.
3-Methoxy-6-methylindan-1-one (3a). 3a was synthesized from
1a. Yield, 43%; yellow crystals. IR (KBr): 2929, 1718, 1284, 1091
1
cm-1. H NMR (300 MHz, CDCl3) (ppm): δ 2.37 (s, 3H), 2.61
Synthesis of 2-Alkoxymethyl-5-methyl-R-chloroacetophenones
(1a-c). Freshly distilled SO2Cl2 (0.45 mL; 5.6 mmol) was added
dropwise to a stirred solution of 2-(alkoxymethyl)-5-methylac-
etophenone (5a-c) (5.6 mmol) in dry methylene chloride (50 mL)
(dd, J1 ) 18 Hz, J2 ) 2.3 Hz, 1H), 2.94 (dd, J1 ) 18 Hz, J2 ) 6.3
Hz, 1H), 3.43 (s, 3H), 4.94 (dd, J1 ) 6.3 Hz, J2 ) 2.3 Hz, 1H),
7.42 (d, J ) 7.9 Hz, 1H), 7.49 (s, 1H), 7.53 (d, J ) 7.9 Hz, 1H).
13C NMR (75.5 MHz) (ppm): δ 21.2, 43.8, 56.9, 76.6, 123.2, 126.2,
136.1, 137.0, 139.7, 150.7, 203.0. MS (EI, 70 eV): m/z ) 176
(M+), 161, 145, 133, 115, 105, 91, 77, 65, 51. Anal. Calcd for
C11H12O2: C, 74.98; H, 6.86. Found: C, 75.08; H, 6.91.
(54) Wagner, P. J.; Kochevar, I. E.; Kemppainen, A. E. J. Am. Chem.
Soc. 1972, 94, 7489-7494.
J. Org. Chem, Vol. 71, No. 21, 2006 8057

Pl´ısˇtil et al.
3-Ethoxy-6-methylindan-1-one (3b). 3b was synthesized from
1b. Yield, 43%; yellow crystals. 1H NMR (300 MHz, CDCl3)
(ppm): δ 1.28 (t, J ) 7.1 Hz, 3H), 2.42 (s, 3H), 2.68 (dd, J1 )
18.5 Hz, J2 ) 2.6 Hz, 1H), 2.95 (dd, J1 ) 18.5 Hz, J2 ) 6.3 Hz,
1H), 3.66 (q, J ) 7.1 Hz, 2H), 5.06 (dd, J1 ) 6.3 Hz, J2 ) 2.6 Hz,
1H), 7.49 (d, J ) 7.9 Hz, 1H), 7.57 (s, 1H), 7.60 (d, J ) 7.9 Hz,
1H). 13C NMR (75.5 MHz) (ppm): δ 15.6, 21.4, 44.7, 65.3, 75.2,
123.3, 126.4, 136.3, 137.2, 139.8, 151.3, 203.5. MS (EI, 70 eV):
m/z ) 190 (M+), 175, 161, 145, 133, 115, 105, 91, 77, 65, 51.
3-(n-Butoxy)-6-methylindan-1-one (3c). 3c was synthesized
from 1c. Yield, 52%; yellow crystals. 1H NMR (300 MHz, CDCl3)
(ppm): δ 0.95 (t, J ) 7.3 Hz, 3H), 1.40-1.45 (m, 2H), 1.59-1.64
(m, 2H), 2.42 (s, 3H), 2.67 (dd, J1 ) 18.5 Hz, J2 ) 2.6 Hz, 1H),
3.00 (dd, J1 ) 18.5 Hz, J2 ) 6.3 Hz, 1H), 3.62 (t, J ) 6.6 Hz, 2H),
5.06 (dd, J1 ) 6.3 Hz, J2 ) 2.6 Hz, 1H), 7.49 (d, J ) 7.9 Hz, 1H),
7.57 (s, 1H), 7.60 (d, J ) 7.9 Hz, 1H). 13C NMR (75.5 MHz)
(ppm): δ 14.0 (broad), 19.5, 21.4, 32.2, 44.6, 69.7, 75.3, 123.3,
126.4, 136.3, 137.2, 139.7, 151.3, 203.4. MS (EI, 70 eV): m/z )
218 (M+), 203, 189, 175, 161, 145, 133, 115, 105, 91, 77, 65, 51.
Preparative Irradiation of 2-(Methoxymethyl)-5-methyl-R-
chloroacetophenone (1a) in Methanol. The stirred solution of
2-(methoxymethyl)-5-methyl-R-chloroacetophenone (1a) (0.5 g; 2.4
mmol) in methanol (200 mL) was purged with argon for 15 min
and irradiated with a 400 W mercury UV lamp through a Pyrex
filter (>280 nm) for 11 h until the conversion was complete (GC).
NaHCO3 (1 g) was then added and the solvent removed under
reduced pressure. The residue was extracted with methylene chloride
(50 mL) and washed two times with water (50 mL) and one time
with brine (50 mL). The organic layer was dried over MgSO4 and
CH2Cl2 was removed in vacuo. The crude product (2-(dimethoxym-
ethyl)-5-methylacetophenone (7a)) was not purified and served for
identification purposes only.
(EI, 70 eV): m/z ) 162 (M+), 147, 134, 119, 105, 91, 77, 65.
Anal. Calcd for C10H10O2: C, 74.06; H, 6.21. Found: C, 73.90; H,
6.23.
Synthesis of 2-(Methoxymethyl)-5-methylphenacyl Benzoate
(1d). 2-(Methoxymethyl)-5-methyl-R-chloroacetophenone (1a) (1.15
g, 5.4 mmol) in acetone (30 mL) was added to a stirred solution of
benzoic acid (1 g, 8.1 mmol), triethylamine (0.9 mL, 6.5 mmol),
and NaI (0.9 g, 6 mmol) in acetone (120 mL) and the reaction
mixture was refluxed for 6.5 h. Acetone was then evaporated in
vacuo and the residue was dissolved in benzene (50 mL) and
washed twice with water (20 mL) and twice with saturated NaHCO3
(20 mL). The combined aqueous layers were washed twice with
benzene (20 mL) and dried over MgSO4 and the solvent was
removed under reduced pressure, yielding a crude product (brown
solid), which was purified by recrystallization (hexane).
2-(Methoxymethyl)-5-methylphenacyl Benzoate (1d). Yield,
1
1.1 g (69%); colorless crystals; mp 47-49 °C (hexane). H NMR
(300 MHz, CDCl3) (ppm): δ 2.42 (s, 3H), 3.44 (s, 3H), 4.70 (s,
2H), 5.44 (s, 2H), 7.35-8.15 (m, 8H). 13C NMR (75.5 MHz)
(ppm): δ 21.2, 58.8, 67.9, 72.5, 128.5, 128.7, 128.8, 129.6, 130.2,
133.2, 133.5, 133.8, 136.9, 137.2, 166.26, 196.2. MS (EI, 70 eV):
m/z ) 299 (M+), 267, 193, 176, 163, 146, 133, 119, 105, 91, 77.
Photochemical Experiments in an NMR Tube. A solution of
the starting material in dry benzene (dried over a 4 Å molecular
sieve) in an NMR tube was purged with argon for 15 min and
irradiated with a 125 W mercury UV lamp through a Pyrex filter
(>280 nm) for 1 h. 1H NMR spectra were measured in the
corresponding time intervals.
Headspace Analyses. The samples were equilibrated in tightly
sealed headspace vials for 24 h, and the head air concentrations of
methyl chloride were measured using GC-MS.
Quantum Chemical Calculations. The quantum chemical
calculations were performed using the Gaussian 03 software
package using density functional theory employing the B3LYP
functional with the 6-31+G** basis set. The wave functions were
checked for internal stability. Ideal gas standard Gibbs free energies
at 298.15 K were estimated using the calculated vibrational
frequencies.
2-(Dimethoxymethyl)-5-methylacetophenone (7a). Yield, 0.4
g (80%); colorless oil. 1H NMR (300 MHz, CDCl3) (ppm): δ 2.40
(s, 3H), 2.56 (s, 3H), 3.37 (s, 6H), 5.79 (s, 1H), 7.28 (d, J ) 7.6
Hz, 1H), 7.29 (s, 1H), 7.56 (d, J ) 7.6 Hz, 1H). 13C NMR (75.5
MHz) (ppm): δ 21.1, 30.4, 54.1, 101.5, 127.3, 128.2, 131.3, 133.9,
138.4, 139.7, 203.9. MS (EI, 70 eV): m/z ) 207 (M+), 193, 177,
161, 145, 133, 115, 105, 91, 77.
Alternative Synthesis of 2-Acetyl-4-methylbenzaldehyde (4).
The mixture of 2-(dimethoxymethyl)-5-methylacetophenone (7a)
(250 mg, 1.2 mmol) in acetone (5 mL) was added to an aqueous
HCl (5%; 20 mL). The mixture was stirred for 5 h until the
conversion was complete (GC). The reaction mixture was then
extracted with methylene chloride (3 × 10 mL). The combined
organic layers were washed with brine (10 mL) and dried over
MgSO4, and CH2Cl2 was removed in vacuo.
Acknowledgment. The project was supported by the Czech
Ministry of Education, Youth and Sport (MSM 0021622413)
and by the Grant Agency of the Czech Republic (203/05/0641).
The authors express their thanks to Jaromir Literak, Ceslav
Ulrich, Aneesh Tazhe Veetil, Jana Klanova, Petr Kulhanek, and
Ctibor Mazal for their help with the synthesis and headspace
analysis and for fruitful discussions.
2-Acetyl-4-methylbenzaldehyde (4). Yield, 150 mg (80%);
colorless solid. IR (KBr): 2921, 2873, 1687, 1602, 1359, 1268,
Supporting Information Available: 1H and 13C NMR spectra
for compounds 1b-d, 3b-c, 5b-c, and 7a. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
1186 cm-1. H NMR (300 MHz, CDCl3) (ppm): δ 2.49 (s, 3H),
2.63 (s, 3H), 7.43 (d, J ) 7.6 Hz, 1H), 7.46 (s, 1H), 7.79 (d, J )
7.6 Hz, 1H), 10.17 (s, 1H). 13C NMR (75.5 MHz) (ppm): δ 21.9,
29.3, 129.1, 130.3, 132.3, 133.5, 141.4, 144.5, 191.9, 201.9. MS
JO061169J
8058 J. Org. Chem., Vol. 71, No. 21, 2006