Solvent dependent photochemical reactions of 3-(2-alkylphenyl)-2,2- dimethyl-3-oxopropanoates and their related compounds

Article abstract of DOI:10.1021/jo981433b

Photochemical reactions of methyl 3-(o-alkylphenyl)-2,2-dimethyl-3- oxopropanoates in hexane gave only the corresponding benzocyclobutenols. However, when irradiation was carried out in methanol, 3-oxonaphthalenones were produced together with the benzocyclobutenols. The ratio of benzocyclobutenol to naphthalenone depends on the bulkiness of the alkyl group in the ortho position. Intermediary 1,4-diradicals or dienols were efficiently trapped by oxygen to afford the corresponding peroxides and/or oxygenated compounds derived from the peroxides.

Full text of DOI:10.1021/jo981433b

J . Org. Chem. 1998, 63, 9013-9018
9013
Solven t Dep en d en t P h otoch em ica l Rea ction s of
3-(2-Alk ylp h en yl)-2,2-d im eth yl-3-oxop r op a n oa tes a n d Th eir
Rela ted Com p ou n d s
Masaichi Saito, Yumiko Kamei, Kanae Kuribara, and Michikazu Yoshioka*
Department of Chemistry, Faculty of Science, Saitama University Shimo-ohkubo,
Urawa, Saitama 338-8570, J apan
Tadashi Hasegawa
Department of Chemistry, Tokyo Gakugei University Nukuikitamachi, Koganei, Tokyo 184-0015, J apan
Received J uly 22, 1998
Photochemical reactions of methyl 3-(o-alkylphenyl)-2,2-dimethyl-3-oxopropanoates in hexane gave
only the corresponding benzocyclobutenols. However, when irradiation was carried out in methanol,
3-oxonaphthalenones were produced together with the benzocyclobutenols. The ratio of benzocy-
clobutenol to naphthalenone depends on the bulkiness of the alkyl group in the ortho position.
Intermediary 1,4-diradicals or dienols were efficiently trapped by oxygen to afford the corresponding
peroxides and/or oxygenated compounds derived from the peroxides.
In tr od u ction
clusively instead of benzocyclobutenols.6 However, irra-
diation of o-alkylphenyl â-keto esters having no
substituents on the alpha position did not afford any
isolable photoproducts,6 though they produce dienols
upon irradiation, as evidenced by deuterium incorpora-
tion.7
The photochemistry of o-alkylphenyl ketones has been
widely explored for a few decades, and a number of
comprehensive reviews have been published.1 The triplet
states of these ketones are transformed into diradicals
via intramolecular hydrogen abstraction, which decay to
short-lived Z- and long-lived E-dienols. The former
undergo a very rapid 1,5-hydrogen shift to regenerate the
starting ketone, while the latter cyclize to give the
benzocyclobutenols.2 It is well-known that the benzocy-
clobutenols from o-alkylphenyl ketones are thermally
unstable and convert quantitatively to the parent ketone
by heating via the dienol as evidenced by trapping
experiments.3 On the other hand, photochemical reac-
tions of 2,6-dialkylphenyl ketones give benzocyclobutenols
efficiently because the large steric congestion in the
triplet diradical results in cyclization rather than the
sterically unfavorable enolization.4 Contrary to the
extensively studied o-alkylphenyl ketones, the photo-
chemistry of o-alkylphenyl 1,3-diketones is still less
explored.5 Irradiation of some o-alkylphenyl 1,3-dike-
tones in methanol gave naphthalenone derivatives ex-
We have already reported that 1-(o-methylphenyl)-2,2-
dimethyl 1,3-diketones underwent photocyclization in
hexane to afford benzocyclobutenols efficiently because
the reverse transfer of hydrogen in the intermediary 1,4-
diradicals to reproduce the starting ketones was sup-
pressed owing to intramolecular hydrogen bonding.8,9 We
also reported on the photochemical reactions of â-hydroxy
ketones in which â-hydrogen abstraction occurred com-
petitively with γ-hydrogen abstraction.10 Because of our
interest in the effect of â-functional groups on the
photoreactivity of o-alkylaryl ketones, we now report
novel selective photochemical reactions of 3-(2-alkyl-
phenyl)-2,2-dimethyl-3-oxopropanoates and their related
compounds having an amide group in the â-position.
Furthermore, the effect of the bulkiness of the ortho and
ester alkyl groups on photoreactivities is reported.
(1) (a) Sammes, P. G. Tetrahedron 1976, 32, 405. (b) Wagner, P. J .
Pure Appl. Chem. 1977, 49, 259. (c) Wagner, P. J . In Rearrangements
in Ground and Excited States; de Mayo, P., Ed.; Academic Press: New
York, 1980; Vol. 3, p 381. (d) Scaiano, J . C. Acc. Chem. Res. 1982, 15,
252.
(2) Wagner, P. J .; Subrahmanyam, D.; Park, B.-S. J . Am. Chem.
Soc. 1991, 113, 709.
Resu lts a n d Discu ssion
Syn th esis of 3-(o-Alk ylp h en yl)-3-oxo Ester s a n d
Am id es. The 3-(2-methylphenyl)-2,2-dimethyl-3-oxopro-
(3) (a) Arnold, B. J .; Sammes, P. G.; Wallace, T. W. J . Chem. Soc.,
Perkin Trans. 1 1974, 409. (b) Arnold, B. J .; Sammes, P. G.; Wallace,
T. W. J . Chem. Soc., Perkin Trans. 1 1974, 415.
(4) (a) Matsuura, T.; Kitaura, Y. Tetrahedron Lett. 1967, 34, 3309.
(b) Matsuura, T.; Kitaura, Y. Tetrahedron 1969, 25, 4487. (c) Ito, Y.;
Umehara, Y.; Hijiya, T.; Yamada, Y.; Matsuura, T. J . Am. Chem. Soc.
1980, 102, 5917. (d) Ito, Y.; Nishimura, H.; Umehara, Y.; Yamada, Y.;
Tone, M.; Matsuura, T. J . Am. Chem. Soc. 1983, 105, 1590. (e) Gue´rin,
B.; J ohnson, L. J . Can. J . Chem. 1989, 67, 473.
(5) In contrast to 1,3-diketones, hydrogen abstraction by the triplet
states of 1,2-diketones has received relatively much attention over the
past two decades. For examples of very recent reports for the
photochemistry of 1,2-diketones, see: (a) Wagner, P. J .; Park, B.-S.;
Sobczak, M.; Frey, J .; Rappoport, Z. J . Am. Chem. Soc. 1995, 117, 7619.
(b) Hasegawa, T.; Imada, M.; Imase, M.; Yamazaki, Y.; Yoshioka, M.
J . Chem. Soc., Perkin Trans. 1 1997, 1271.
(6) Hornback, J . M.; Poundstone, M. L.; Vadlamani, B.; Graham, S.
M.; Gabay, J .; Patton, S. T. J . Org. Chem. 1988, 53, 5597.
(7) â-Keto esters have been reported to undergo the Norrish type II
reaction, see: Hasegawa, T.; Arata, Y.; Endoh, M.; Yoshioka, M.
Tetrahedron 1985, 41, 1667.
(8) (a) Yoshioka, M.; Arai, M.; Nishizawa, K.; Hasegawa, T. J . Chem.
Soc., Chem. Commun. 1990, 374. (b) Yoshioka, M.; Nishizawa, K.; Arai,
M.; Hasegawa, T. J . Chem. Soc., Perkin Trans. 1 1991, 541. (c)
Yoshioka, M.; Momose, S.; Nishizawa, K.; Hasegawa, T. J . Chem. Soc.,
Perkin Trans. 1 1992, 499.
(9) Solvation of a hydroxy radical results in the enhancement of the
quantum efficiency with which valerophenone undergoes photoelimi-
nation in solution. Wagner, P. J . J . Am. Chem. Soc. 1967, 89, 5898.
(10) (a) Yoshioka, M.; Miyazoe, S.; Hasegawa, T. J . Chem. Soc.,
Chem. Commun. 1992, 418. (b) Yoshioka, M.; Miyazoe, S.; Hasegawa,
T. J . Chem. Soc., Perkin Trans. 1 1993, 2781.
10.1021/jo981433b CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/10/1998

9014 J . Org. Chem., Vol. 63, No. 24, 1998
Saito et al.
Sch em e 1
Sch em e 2
Ta ble 1. Yield s of P h otop r od u cts in th e P h otor ea ction s
of â-Keto Ester s
yields (%)
â-keto ester
solvent
9
10
4a
4e
4f
methanol
methanol
methanol
23
25
9
32
100
panoates 4a -d were prepared by the Reformatsky reac-
tion of o-tolualdehyde (1) with 2-bromoalkanoates 2
followed by J ones oxidation and methylation. The 3-(2,4-
dialkylphenyl)-3-oxo esters 4e and 4f were obtained via
the condensation of the corresponding substituted ac-
etophenones 5a and 5b with dimethyl carbonate 6
followed by methylation.
N,N-Diethyl-3-(2-methylphenyl)-2,2-dimethyl-3-oxo-
propanamide (4g) was prepared in a poor yield from the
corresponding â-keto amide 7. 3-(2-Methylphenyl)-2,2-
dimethyl-3-oxopropanamide (4h ) and 3-phenyl-2,2-di-
methyl-3-oxopropanamide (4i) were synthesized by hy-
drolysis of the corresponding â-keto nitriles 8.
Ir r a d ia t ion of Met h yl 3-(2-Alk ylp h en yl)-2,2-d i-
m eth yl-3-oxop r op a n oa tes: Effect of Bu lk in ess of
Or th o Alk yl Su bstitu en ts on P h otor ea ctivities. Ir-
radiation of methyl 3-o-tolyl-2,2-dimethyl-3-oxopropanoate
(4a ) in methanol with a high-pressure mercury lamp
through a Pyrex filter gave the oxonaphthalenone 9a
(23%) as the major product together with the benzo-
cyclobutenol 10a (9%) at 94% conversion, in contrast to
Hornback’s report that naphthalenone derivatives were
obtained exclusively in the photochemical reactions of
o-tolyl 1,3-diketones in methanol.6 The yields of photo-
products 9 and 10 are given in Table 1. The benzo-
cyclobutenol 10a is probably formed from the E-enol
resulting from an intermediary triplet diradical.2 The
formation of 9a is rationalized in terms of intramolecular
trapping of the benzyl radical moiety by the ester
carbonyl carbon followed by hydrogen shift and elimina-
tion of methanol8b or by cyclization of the E-enol.6 We
have already found that naphthalenone derivatives were
obtained as major products in the photochemical reac-
tions of 3-alkyl and 3-aryl-substituted 1-o-tolyl-2,2-di-
methyl 1,3-diketones in methanol together with benzo-
4a
4e
4f
hexane
hexane
hexane
70
82
73
cyclobutenols.8b In the present case, however, the prod-
uct ratio of 10a to 9a is higher than those of the previous
results observed in o-tolyl 1,3-diketones, probably due to
the less electrophilic nature of ester carbon moiety in 4a .
Irradiation of the 3-o-ethylphenyl-3-oxo ester 4e under
the same conditions gave the naphthalenone 9e and the
benzocyclobutenol 10e in 25 and 32% yields, respectively.
On the other hand, photochemical reaction of the â-keto
ester 4f bearing an isopropyl group in the ortho position
in methanol exclusively afforded benzocyclobutenol 10f
(100%). Thus, the ratio of the naphthalenone 9 to the
benzocyclobutenol 10 became lower with the bulkier
ortho alkyl group, reflecting the steric hindrance leading
to 9. Contrary to the photoreactions of 4a ,e,f in metha-
nol, irradiation of them in hexane gave benzocyclobutenols
10a ,e,f exclusively, as was observed in our previous
reports.8,10
Ir r a d ia tion of Va r iou s Alk yl Ester s of 3-(2-Meth -
ylp h en yl)-2,2-d im eth yl-3-oxop r op a n oic Acid s: Ef-
fect of Bu lk in ess of t h e E st er Gr ou p on P r od u ct
Distr ibu tion . Effect of bulkiness of the ester group on
product distribution was also investigated. Irradiation
of the ethyl 4b, isopropyl 4c and tert-butyl 4d esters of
3-(2-methylphenyl)-2,2-dimethyl-3-oxopropanoic acid in
methanol gave benzocyclobutenols 10b (11%), 10c (35%),
and 10d (69%), respectively, along with the naphthale-
none 9a (27% from 4b, 15% from 4c, and 3% from 4d ),
reflecting perhaps the less favorable reaction of the
benzyl radical site with the ester carbonyl carbon having
the bulky alkyl group because of the sterically repulsive
interaction.

Solvent Dependent Photochemical Reactions
J . Org. Chem., Vol. 63, No. 24, 1998 9015
Sch em e 3
Sch em e 6
Sch em e 4
Sch em e 5
in hexane oxygen has more access to the intermediate
because of intermolecular hydrogen bonding. This type
of remarkable solvent effect has not been reported in
irradiation of o-alkylphenyl ketones in the presence of
oxygen. Photooxidation of the o-alkylphenyl ketones
proceeds in both methanol and hexane.11a,14
In the photochemical reactions of 4a and 4e in hexane
under air-bubbling, intermediary peroxides 11b and 11c
readily underwent dehydration to give the aldehyde 12
and the ketone 13, respectively. The aldehyde 12 un-
derwent further reaction to yield the phthalide 14 under
the irradiation conditions.12
P h otoch em ica l Rea ction s of 3-(2-Meth ylp h en yl)-
2,2-d im eth yl-3-oxop r op a n a m id es. The photochemis-
try of o-tolyl â-oxopropanamides has also been a subject
of interest. N-Alkyl â-oxo amides are known to undergo
photocyclization through hydrogen shift from the carbon
next to the nitrogen to the ketone carbonyl oxygen.15 In
the course of our study on the effect of â-functionality on
the photoreactions of o-alkylphenyl ketones, we chose an
N,N-disubstituted 3-oxopropanamide 4g because of the
presence of two kinds of hydrogens abstractable by the
ketone carbonyl oxygen: one is the γ-hydrogen in the
2-methylphenyl group and the other is the δ-hydrogen
on the carbon next to the nitrogen.
Ir r a d ia t ion of Met h yl 1-(o-Alk ylp h en yl)-2,2-d i-
m eth yl-3-oxop r op a n oa tes in th e P r esen ce of Oxy-
gen . Irradiation of 4f in hexane under air-bubbling gave
the peroxide 11a (40%) and the benzocyclobutenol 10f
(42%) at 52% conversion. Although the formation of 11a
is reasonably explained by the reaction of the intermedi-
ate 1,4-diradical or dienol with oxygen,11,12 it is still
ambiguous whether the oxidation involves the triplet-
state dienol or the ground-state dienol.13 Interestingly,
the oxidation was effectively suppressed [10f (73%), 11a
(5%)] in methanol probably due to solvation of the
intermediate by methanol to protect it from oxygen, while
(11) For example, see: (a) Kitaura, Y.; Matsuura, T. Tetrahedron
1971, 27, 1597. (b) Lutz, H.; Breheret, E.; Lindqvist, L. J . Chem. Soc.,
Faraday Trans. 1 1973, 69, 2096. (c) Findlay, D. M.; Tchir, M. F. J .
Chem. Soc., Faraday Trans. 1 1976, 72, 1096. (d) Haag, R.; Wirz, J .;
Wagner, P. J . Helv. Chim. Acta 1977, 60, 2595. (e) Small, R. D., J r.;
Scaiano, J . C. J . Am. Chem. Soc. 1977, 99, 7713. (f) Viriot-Villaume,
M.-L.; Carre´, M.-L.; Caube`re, P. J . Chem. Soc., Perkin Trans. 1 1979,
1395. (g) Carre´, M.-L.; Viriot-Villaume, M.-L.; Caube`re, P. J . Chem.
Soc., Perkin Trans. 1 1979, 2542.
(12) We have already reported similar photochemical reactions in
the presence of oxygen, see: Yoshioka, M.; Nishizawa, K.; Suzuki, J .;
Iwata, Y.; Kumakura, S.; Hasegawa, T. J . Chem. Soc., Perkin Trans.
1 1995, 3097.
(13) In the absence of light, dienols derived from benzocyclobutenols
by heating are known to react with oxygen. (a) Yang, N. C.; Rivas, C.
J . Am. Chem. Soc. 1961, 83, 2213. (b) Heindel, N. D.; Sarver, E. W.;
Pfau, M. Tetrahedron Lett. 1968, 3579. (c) Porter, G.; Tchir, M. F. J .
Chem. Soc. A 1971, 3772. (d) Pfau, M.; Sarver, E. W.; Heindel. N. D.
Bull. Soc. Chim. Fr. 1973, 183.
(14) For example, see: Ito, Y.; Matsuura, T. J . Am. Chem. Soc. 1983,
105, 5237, and references therein.
(15) The photochemical reactions of N,N-disubstituted benzoyl-
acetamide, see: (a) Hasegawa, T.; Aoyama, H.; Omote, Y. J . Chem.
Soc., Perkin Trans. 1 1976, 2054. (b) Hasegawa, T.; Aoyama, H.; Omote,
Y. J . Chem. Soc., Perkin Trans. 1 1979, 963.

9016 J . Org. Chem., Vol. 63, No. 24, 1998
Saito et al.
20% sulfuric acid and extracted with ether. The ethereal
extract was washed successively with saturated sodium chlo-
ride and sodium hydrogencarbonate solutions and dried over
anhydrous magnesium sulfate. After the volatile substances
were removed, the resulting crude hydroxy ester 3a was
dissolved in acetone (30 mL). To this solution was added
dropwise 13 mL of 2.67 M J ones reagent at 5 °C, and the
mixture was allowed to stand overnight. After the acetone
was removed, the residue was extracted with ether. The
ethereal solution was washed with sodium hydrogencarbonate
solution. After the ether was removed, the residue was
chromatographed on silica gel using a mixture of hexane and
ethyl acetate (4:1) as eluent to afford the crude â-keto ester
(3.62 g). To sodium hydride (1.50 g, 37.5 mmol as 60% assay)
in a mixed solvent (benzene:DMF ) 2:1; 30 mL) was added a
solution of the â-keto ester (3.62 g) in the same solvent (30
mL). After 30 min of stirring, methyl iodide (2.35 mL, 37.7
mmol) was added, and the mixture was allowed to stand for 2
h at ambient temperature. Saturated ammonium chloride
solution was added to the mixture, and an organic layer was
extracted with ether. After the solvent was removed, the
residue was subjected to chromatography on silica gel (hexane:
ethyl acetate ) 9:1) to give methyl 3-(2-methylphenyl)-2,2-
dimethyl-3-oxopropanoate (4a ) (2.27 g, 64%). For 4a : 1H
NMR(400 MHz) δ 1.50(s, 6H), 2.35(s, 3H), 3.63(s, 3H), 7.15-
7.19(m, 1H), 7.23-7.26(m, 2H), 7.28-7.32(m, 1H); 13C NMR-
(100 MHz) δ 20.5(q), 23.6(q), 52.3(q), 55.6(s), 125.1(d), 125.5(d),
Sch em e 7
Irradiation of N,N-diethyl 3-(2-methylphenyl)-2,2-di-
methyl-3-oxopropanamide (4g) in methanol exclusively
furnished the corresponding benzocyclobutenol 10g, re-
flecting the preference of hydrogen abstraction from γ to
δ because of the more negative entropy of activation in
the six-membered ring than that in the seven-membered
ring transition state.15 In the presence of oxygen, the
phthalide 15 was obtained together with the benzo-
cyclobutenol 10g. The phthalide 15 must be formed from
the initially formed peroxide.8b,13
130.1(d), 131.5(d), 136.8(s), 137.9(s), 174.5(s), 204.0(s); IR(cm-1
)
1734(CdO), 1692(CdO). Anal. Calcd for C13H16O3: C, 70.89;
H, 7.32. Found: C, 70.5; H, 7.4.
The photochemistry of the parent 3-oxopropanamides
was also investigated. Irradiation of 3-(2-methylphenyl)-
2,2-dimethyl-3-oxopropanamide 4h in methanol gave the
benzocyclobutenol 10h exclusively through the abstrac-
tion of hydrogen from the o-methyl group. In the
photoreaction of 4g and 4h , however, the naphthalenone
9a was not produced, in contrast to that of methyl 3-(2-
methylphenyl)-2,2-dimethyl-3-oxopropanoate (4a ), per-
haps due to the reduced ability of the amino group as a
leaving group compared to the methoxy group. Finally,
the photolysis of 3-phenyl-2,2-dimethyl-3-oxopropana-
mide 4i resulted in a complex mixture, in which no
identifiable product was obtained.
In conclusion, the photochemical reactions of 3-(2-
alkylphenyl)-2,2-dimethyl-3-oxopropanoates gave two types
of products, benzocyclobutenols and 3-oxonaphthale-
nones. The product ratio depends on the bulkiness of
both 2- and ester alkyl groups as well as solvent polarity.
Photooxidation of these esters proceeds more efficiently
in hexane than in methanol. These novel selectivities
are worthy to note not only from the mechanistic but also
from a synthetic point of view. In the photolysis of 3-(2-
methylphenyl)-2,2-dimethyl-3-oxopropanamides, 1,4-cy-
clization occurs in preference to 1,5-cyclization.
Compounds 4b-d were prepared from o-tolualdehyde and
ethyl 2-bromo-2-methylpropanoate (2b), isopropyl 2-bromopro-
propanoate (2c), and tert-butyl 2-bromopropanoate (2d ), re-
spectively, by the similar procedures as above. The isopropyl
ester 2c was prepared from 2-bromopropanoic acid and 2-pro-
panol in the presence of concentrated sulfuric acid and tert-
butyl ester 2d was prepared from 2-bromopropanoyl bromide
and tert-butyl alcohol in the presence of N,N-dimethylaniline.16
P r ep a r a tion s of â-Oxo Ester s 4e,f. To a suspension of
sodium hydride (824 mg, 22.3 mmol as 65% assay) in THF
(15 mL) was added a THF (5 mL) solution of 2,4-diethyl-
acetophenone (5a ) (3.89 g, 22.1 mmol). After several hours of
stirring at room temperature, dimethyl carbonate (6) (2.5 mL,
28.9 mmol) was added, and the mixture was heated under
reflux for 1.5 h. Saturated ammonium chloride solution was
added to the mixture, and an organic layer was extracted with
ether. After the solvent was removed, the residue was purified
by chromatography on silica gel (hexane:ethyl acetate ) 10:1)
to afford the corresponding â-keto ester (3.832 g). This ester
was methylated with methyl iodide to give methyl 3-(2,4-
diethylphenyl)-2,2-dimethyl-3-oxopropanoate (4e) (2.32 g, 40%)
by the same procedure as that for the preparation of 4a . For
4e: 1H NMR(400 MHz) δ 1.20-1.25(m, 6H), 1.50(s, 6H), 2.61-
2.70(m, 4H), 3.63(s, 3H), 6.99(d, J ) 8 Hz, 1H), 7.10(s, 1H),
7.19(d, J ) 8 Hz, 1H); 13C NMR(100 MHz) δ 15.1(q), 16.0(q),
23.9(q), 26.9(t), 28.7(t), 52.3(q), 55.4(s), 124.5(d), 126.0(d),
129.8(d), 134.7(s), 143.7(s), 146.8(s), 174.8(s), 203.6(s); IR(cm-1
)
1742(CdO), 1694(CdO). Anal. Calcd for C16H22O3: C, 73.25;
H, 8.45. Found: C, 73.1; H, 8.5.
Exp er im en ta l Section
Compound 4f was prepared from 2,4-diisopropylacetophe-
none (5b) and dimethyl carbonate as the same procedure as
above.
Gen er a l P r oced u r e. All irradiations were carried out by
using a 100 W or a 450 W high-pressure mercury lamp. 1H
NMR (400, 200 MHz) and 13C NMR (100, 50 MHz) spectra
were recorded in CDCl3 with tetramethylsilane as an internal
standard. IR spectra were recorded for solutions in CCl4. Wet
column chromatography (WCC) was carried out with Merck
Kieselgel 60. Melting points were uncorrected and boiling
points were estimated from the oven temperature in Kugelrohr
distillation.
P r ep a r a tion of â-Oxo Ester s 4a -d . Compounds 4a -d
were prepared via the Reformatsky reaction. A benzene (16
mL) solution of o-tolualdehyde (1) (5.75 mL, 49.7 mmol) and
methyl bromoacetate (2a ) (4.70 mL, 49.6 mmol) was added to
zinc powder (4.58 g, 70.1 mmol) in refluxing benzene (10 mL).
After 5 h of refluxing, the mixture was poured into aqueous
P r ep a r a tion of â-Oxo Am id e 4g. A mixture of methyl
o-toluoyl acetate (966 mg, 5.03 mmol) and diethylamine (1 mL,
9.67 mmol) was heated at 150 °C for 14 h. The resulting
viscous oil was subjected to chromatography on silica gel
(hexane:ethyl acetate ) 5:1) to give 7 (891 mg, 76%). The
amide 7 was methylated with methyl iodide by the same
procedure as that for the preparation of 4a . Chromatography
of the crude mixture on silica gel (hexane:ethyl acetate ) 3:1)
gave N,N-diethyl-3-(2-methylphenyl)-2,2-dimethyl-3-oxopro-
1
panamide (4g) (80 mg, 8%). For 4g: mp 43 °C (hexane); H
(16) Vollmar, A.; Dunn, M. S. J . Org. Chem. 1960, 25, 387.

Solvent Dependent Photochemical Reactions
J . Org. Chem., Vol. 63, No. 24, 1998 9017
Ta ble 2. Meth od s for Ir r a d ia tion of â-Oxo Ester s 4a -f a n d Am id es 4g-i
â-oxo
esters or
amides
solvent used
for WCC
(hexane:AcOEt)
irradiation
period
convn
(%)
solvent
mg/mL
method
product yields (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4a
4e
4f
4a
4e
4f
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
hexane
hexane
hexane
hexane
hexane
hexane
MeOH
MeOH
602/120
608/120
605/120
604/120
261/30
3 ha
A
A
A
A
A
D
D
D
A
D
A
A
C
B
B
B
C
97
92
95
6:1
4:1
4:1
6:1
10:1
9a (23%), 10a (9%)
9a (27%), 10b (11%)
9a (15%), 10c (35%)
9a (3%), 10d (69%)
9e (25%), 10e (32%)
10f (100%)
10g (63%)
10h (75%)
complex mixture
10a (70%)
10e (82%)
10f (73%)
10a (67%), 14 (6%)
13 (38%)
10f (42%), 11a (40%)
10f (73%), 11a (5%)
10g (21%), 15 (46%)
3 ha
5 ha
5 ha
93
3 ha
100
100
100
100
100
94
100
58
94
100
52
100
63
177/2
80/2
17 db
10 db
10 db
3 da
5:1
1:3
1:3
6:1
8:1
8:1
6:1
6:1
8:1
8:1
2:1
101/1.5
153/140
181/1.5
413/25
1189/350
596/120
190/30
1306/350
1039/350
195/80
4 db
19.5 ha
8 db
6 ha
13 ha
12 db
5 db
4f
4g
20 ha
a
b
A 100 W high-pressure mercury lamp was used. A 450 W high-pressure mercury lamp was used.
NMR(200 MHz) δ 0.85(br t, J ) 7 Hz, 3H), 0.97(br t, J ) 7
Hz, 3H), 1.52(s, 6H), 2.50(s, 3H), 2.95(br q, J ) 7 Hz, 2H),
3.31(br q, J ) 7 Hz, 2H), 7.17-7.35(m, 3H), 7.67(br d, J ) 6
Hz, 1H); 13C NMR(50 MHz) δ 11.7(q), 13.2(q), 21.9(q), 25.6(q).
40.0(t), 41.3(t), 55.4(s), 125.3(d), 128.8(d), 131.5(d), 132.3(d),
135.4(s), 139.6(s), 172.6(s), 203.5(s); IR(cm-1) 1683(CdO),
1635(Et2NCdO). Anal. Calcd for C16H23NO2: C, 73.53; H,
8.86; N, 5.36. Found: C, 73.6; H, 9.0; N, 5.4.
graphed on silica gel. The irradiation conditions and the
solvent used for chromatography are shown in Table 2.
2,2-Dim e t h yl-3-o xo -3,4-d ih yd r o n a p h t h a le n -1(2H )-
on e (9a ): mp 60-61 °C (hexane); 1H NMR(400 MHz) δ 1.43-
(s, 6H), 3.98(s, 2H), 7.31(d, J ) 8 Hz, 1H), 7.41-7.44(m, 1H),
7.57-7.60(m, 1H), 8.09(d, J ) 8 Hz, 1H); 13C NMR(100 MHz)
δ 21.4(q), 41.4(t), 59.4(s), 127.5(d), 128.1(d), 128.4(d), 130.2-
(s), 134.2(d), 136.2 (s), 198.9 (s), 206.7(s); IR(cm-1) 1730-
(CdO), 1690(CdO). Anal. Calcd for C12H12O2: C, 76.58; H,
6.42. Found: C, 76.4; H, 6.3.
P r ep a r a tion s of â-Oxo Am id es 4h ,i. To a THF (20 mL)
solution of lithium diisopropylamide which was prepared from
diisopropylamine (0.8 mL, 5.69 mmol) and butyllithium (1.66
M in hexane; 3.90 mL) was added isobutylnitrile (0.52 mL,
5.72 mmol) at -70 °C. The mixture was warmed to -10 °C
and treated with o-tolualdehyde (1) (0.65 mL, 5.62 mmol).
After usual workup, the mixture was subjected to chromatog-
raphy on silica gel (hexane:ethyl acetate ) 2:1) to afford 8a
(788 mg, 74%). To an acetone (5 mL) solution of 8a (100 mg,
0,53 mmol) was added 0.2 mL of 2.67 M J ones reagent. After
usual workup, the mixture was chromatographed on silica gel
(hexane:ethyl acetate ) 10:1) to afford the corresponding
â-keto nitrile (82 mg, 83%). A suspension of the â-keto nitrile
(646 mg, 3.43 mmol) in water (1 mL) was heated at 85 °C for
19 h in the presence of 5 mL of concentrated sulfuric acid. The
mixture was poured into ice water, and an organic layer was
extracted with ether. After the solvent was removed, the
residual solid was recrystallized (hexane + ethyl acetate) to
give 3-(2-methylphenyl)-2,2-dimethyl-3-oxopropanamide (4h )
(440 mg, 66%). For 4h : mp 86 °C (hexane + ethyl acetate);
1H NMR (400 MHz) δ 1.45(s, 6H), 2.31(s, 3H), 6.15(br s, 2H),
7.17(t, J ) 7 Hz, 1H), 7.23(d, J ) 7 Hz, 1H), 7.28-7.34(m,
2H); 13C NMR(100 MHz) δ 20.1(q), 24.0(q), 55.7(s), 125.2(d),
125.8(d), 130.1(d), 131.3(d), 135.8(s), 138.2(s), 174.7(s), 208.1-
(s); IR(cm-1) 3480(NH), 1700(CdO), 1684(NH2CdO). Anal.
Calcd for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C,
70.2; H, 7.4; N, 6.8.
6-Eth yl-2,2,4-tr im eth yl-3-oxo-3,4-d ih yd r on a p h th a len -
1(2H)-on e (9e): 1H NMR(400 MHz) δ 1.28(t, J ) 8 Hz, 3H),
1.40(s, 3H), 1.44(s, 3H), 1.59(d, J ) 7 Hz, 3H), 2.74(q, J ) 8
Hz, 2H), 4.03(q, J ) 7 Hz, 1H), 7.21-7.24(m, 2H), 7.98(d, J )
8 Hz, 1H); 13C NMR(100 MHz) δ 14.9(q), 15.4(q), 19.6(q),
24.9(q), 29.1(t), 43.4(d), 58.2(s), 126.0(d), 127.1(d), 128.1(s),
128.1(d), 141.5(s), 151.6(s), 199.4(s), 209.6(s); IR(cm-1
)
1732(CdO), 1684(CdO). A satisfactory chemical analysis of
9e was not obtained because of its instability. It decomposes
to yellow viscous oil.
Meth yl 2-(1′-Hyd r oxy-1′,2′-d ih yd r oben zocyclobu ten -1′-
yl)-2-m eth ylp r op a n oa te (10a ): bp 91-94 °C(0.4 mmHg); 1H
NMR(400 MHz) δ 1.22(s, 3H), 1.26(s, 3H), 3.09(d, J ) 14 Hz,
1H), 3.50(d, J ) 14 Hz, 1H), 3.70(br s, 1 H), 3.77(s, 3H), 7.1-
7.3(m, 4H); 13C NMR(100 MHz) δ 20.9(q), 21.4(q), 42.4(t), 47.7-
(s), 51.8(q), 84.1(s), 121.9(d), 123.1(d), 126.9(d), 129.1(d),
142.0(s), 147.0(s), 177.7 (s); IR(cm-1) 3500(OH), 1720(CdO).
Anal. Calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 70.8;
H, 7.3.
Meth yl 2-(4′-Eth yl-1′-h yd r oxy-1′,2′-d ih yd r o-2′-m eth yl-
b en zocyclob u t en -1′-yl)-2-m et h ylp r op a n oa t e (10e): 1H
NMR(400 MHz) δ 1.09(s, 3H), 1.22(t, J ) 8 Hz, 3H), 1.37(d, J
) 8 Hz, 3H), 1.46(s, 3H), 2.63(q, J ) 8 Hz, 2H), 3.64(q, J ) 8
Hz, 1H), 3.79(s, 3H), 4.25(s, 1H), 6.98(s, 1H), 7.04(d, J ) 8
Hz, 1H), 7.12(d, J ) 8 Hz, 1H); 13C NMR(100 MHz) δ 14.6(q),
15.9(q), 22.3(q), 24.7(q), 29.6(t), 46.9(s), 52.0(q), 54.0(d), 85.6-
(s), 121.1(d), 121.5(d), 127.0(d), 142.0(s), 145.9(s), 146.9(s),
179.0(s); IR(cm-1) 3504(OH), 1714(CdO). Anal. Calcd for
Compound 4i was prepared from isobutylnitrile and benz-
aldehyde by the same procedure as above.
Gen er a l P r oced u r es for P h otolysis of â-Oxo Ester s
4a -f a n d â-Oxo Am id es 4 g-i. Irradiations were carried
out by four different methods. Method A: A solution of 4 was
placed in a glass vessel into which was placed a Pyrex water
jacket to cool a lamp inserted in it and irradiated under argon.
Method B: A solution of 4 was placed in a glass vessel in the
same manner as method A and irradiated under bubbling air.
Method C: A solution of 4 was placed in a glass vessel in the
same manner as method A and irradiated without bubbling
any gas. Method D: A solution of 4 was placed in a Pyrex
tube and degassed by freeze-pump-thaw cycles, and the tube
was sealed. The tube was placed on the wall of the Pyrex
water jacket into which was placed a lamp. After irradiation,
the solvent was removed and the residue was chromato-
C
16H22O3: C, 73.25; H, 8.45. Found: C, 72.7; H, 8.5.
Meth yl 2-(1′-Hyd r oxy-4′-isop r op yl-1′,2′-d ih yd r o-2′,2′-
d im e t h ylb e n zocyclob u t e n -1′-yl)-2-m e t h ylp r op a n oa t e
(10f): 1H NMR(400 MHz) δ 1.09(s, 3H), 1.23(d, J ) 7 Hz, 6H),
1.36(s, 6H), 1.53(s, 3H), 2.87(sept, J ) 7 Hz, 1H), 3.75(s, 3H),
3.79(s, 1H), 6.95(s, 1H), 7.06(d, J ) 7 Hz, 1H), 7.16(d, J ) 7
Hz, 1H); 13C NMR(100 MHz) δ 23.0(q), 23.3(q), 24.1(q), 24.2-
(q), 25.9(q), 26.9(q), 34.8(d), 47.6(s), 51.9(q), 54.0(s), 87.0(s),
117.8(d), 122.0(d), 125.8(d), 141.3(s), 150.5(s), 152.4(s), 179.2-
(s); IR(cm-1
18H26O3: C, 74.45; H, 9.02. Found: C, 74.4; H, 9.1.
N,N-Diethyl2-(1′-Hydroxy-1′,2′-dihydrobenzocyclobuten-
1′-yl)-2-m eth ylp r op a n a m id e (10 g). 1H NMR(400 MHz) δ
) 3516(OH), 1712(CdO). Anal. Calcd for
C

9018 J . Org. Chem., Vol. 63, No. 24, 1998
Saito et al.
1.19(br t, J ) 7 Hz, 6H), 1.31(s, 3H), 1.34(s, 3H), 3.15(d, J )
14 Hz, 1H), 3.40(d, J ) 14 Hz, 1H), 3.35-3.52(m, 4H), 5.35(s,
1H), 7.11(d, J ) 7 Hz, 1H), 7.18-7.24(m, 3H); 13C NMR(100
MHz) δ 13.3(q), 20.8(q), 21.4(q), 41.8(t), 42.4(t), 47.1(s), 86.8-
(s), 122.5(d), 123.1(d), 127.0(d), 128.9(d), 142.7(s), 148.1(s),
177.2(s); IR(cm-1) 3450(OH), 1611(CdO). Anal. Calcd for
C16H23NO2: C, 73.53; H, 8.87; N, 5.36. Found: C, 72.8; H,
9.0; N, 5.1.
Meth yl 2-(1′-Hyd r oxy-6′-isop r op yl-4′,4′-d im eth yl-1′,4′-
d ih yd r ob en zo[d ][1,2]d ioxin -1′-yl)-2-m et h ylp r op a n oa t e
(11a ): 1H NMR(400 MHz) δ 1.08(s, 3H), 1.25(d, J ) 7 Hz, 6H),
1.48(s, 3H), 1.56(s, 3H), 1.65(s, 3H), 2.90(sept, J ) 7 Hz, 1H),
3.78(s, 3H), 5.64(s, 1H), 7.00(d, J ) 2 Hz, 1H), 7.12(dd, J ) 2
and 8 Hz, 1H), 7.43(d, J ) 8 Hz, 1H); 13C NMR(100 MHz) δ
21.6(q), 23.8(q), 23.8(q), 23.8(q), 26.4(q), 26.6(q), 33.9(d), 50.5-
(s), 52.6(q), 80.6(s), 103.2(s), 121.9(d), 124.3(d), 125.8(d), 129.0-
(s), 142.1(s), 149.0(s), 177.1(s); IR(cm-1) 3648(OH), 1710(Cd
O). A satisfactory elemental analysis of 11a could not be
achieved because of its instability.
Meth yl 3-(2-Acetyl-4-eth ylp h en yl)-2,2-d im eth yl-3-oxo-
p r op a n oa te (13): 1H NMR(400 MHz) δ 1.28(t, J ) 8 Hz, 3H),
1.54(s, 6H), 2.53(s, 3H), 2.72(q, J ) 8 Hz, 2H), 3.68(s, 3H),
7.29-7.36(m, 2H), 7.48(s, 1H); 13C NMR(100 MHz) δ 15.1(q),
23.5(q), 27.8(q), 28.6(t), 52.4(q), 55.1(s), 126.8(d), 128.2(d),
130.8(d), 136.8(s), 138.9(s), 146.6(s), 174.5(s), 200.4(s), 203.9-
(s). Anal. Calcd for C16H20O4: C, 69.55; H, 7.30. Found: C,
69.7; H, 7.4.
(s), 175.3(s); IR(cm-1) 1780(CdO), 1730(CdO). Anal. Calcd
for C13H14O4: C, 66.66; H, 6.02. Found: C, 66.5; H, 6.1.
N,N-Dieth yl 2-Meth yl-2-p h th a lid ylp r op a m id e (15): mp
106 °C (hexane + benzene); 1H NMR(400 MHz) δ 0.84(s, 3H),
1.19(br t, J ) 8 Hz, 6H), 1.58(s, 3H), 3.34-3.41(m, 2H), 3.54-
(br s, 2H), 6.10(s, 1H), 7.48-7.52(m, 1H), 7.60-7.62(m, 2H),
7.87(d, J ) 8 Hz, 1H); 13C NMR(100 MHz) δ 13.3(q), 18.0(q),
23.7(q), 41.7(t), 46.5(s), 86.0(d), 125.0(d), 125.0(d), 127.2(s),
128.9(d), 133.9(d), 148.3(s), 170.7(s), 173.9(s); IR(cm-1) 1772-
(CdO), 1621(CdO). Anal. Calcd for C16H21NO3: C, 69.79; H,
7.69; N, 5.09. Found: C, 69.9; H, 7.7; N, 5.1.
Ir r a d ia tion of 3-P h en yl-2,2-d im eth yl-3-oxop r op a n a -
m id e (4i) in Met h a n ol. A methanol solution (140 mL) of
3-phenyl-2,2-dimethyl-3-oxopropanamide (4i) (153 mg, 0.80
mmol) was irradiated for 3 days. From the irradiation
mixture, no identifiable products were isolated by chromatog-
raphy.
Ack n ow led gm en t. This work was partially sup-
ported by a Grant-in Aid for Scientific Research (C) No.
08640668 (M. Y.) from the Ministry of Education,
Science, Sports and Culture, J apan.
Su p p or tin g In for m a tion Ava ila ble: Physical properties
1
of compounds 4b-d , f, i and 10b-d , h , and H and 13C NMR
spectra for compounds 9e and 11a (7 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
Meth yl 2-Meth yl-2-p h th a lid ylp r op a n oa te (14): bp 97-
100 °C (0.4 mmHg); 1H NMR(400 MHz) δ 1.01 (s, 3H), 1.36 (s,
3H), 3.81(s, 3H), 5.80(s, 1H), 7.35(d, J ) 8 Hz, 1H), 7.55(t, J
) 8 Hz, 1H), 7.65(t, J ) 8 Hz, 1H), 7.91 (d, J ) 8 Hz, 1H); 13
C
NMR(100 MHz) δ 18.4(q), 22.6(q), 46.7(s), 52.3(q), 84.3(d),
122.8(d), 125.8(d), 126.9(s), 129.4(d), 134.0(d), 147.0(s), 170.1-
J O981433B