Synthesis of naphthalenes using acid-catalyzed ring-opening and recyclization of 3-acetyl-5,5-diaryl-2-methyl-4,5-dihydrofurans. Isolation of intermediates

Article abstract of DOI:10.1016/S0040-4039(01)00431-2

3-Acetyl-5,5-diaryl-2-methyl-4,5-dihydrofurans were heated in concentrated hydrochloric acid to give the 4-aryl-1-methylnaphthalenes in high yields. The same reaction was carried out in hydrochloric acid diluted with acetonitrile to give the 5,5-diaryl-4-

Full text of DOI:10.1016/S0040-4039(01)00431-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3351–3354
Synthesis of naphthalenes using acid-catalyzed ring-opening and
recyclization of 3-acetyl-5,5-diaryl-2-methyl-4,5-dihydrofurans.
Isolation of intermediates
Shougo Kajikawa,a Hiroshi Nishinob,* and Kazu Kurosawac
aDepartment of Environmental Science, Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1,
Kumamoto 860-8555, Japan
bInstitute for Fundamental Research of Organic Chemistry (IFOC), Kyushu University, Hakozaki 6-10-1, Higashi-ku,
Fukuoka 812-8581, Japan
cDepartment of Environmental Science, Faculty of Science, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan
Received 29 January 2001; revised 12 March 2001; accepted 14 March 2001
Abstract—3-Acetyl-5,5-diaryl-2-methyl-4,5-dihydrofurans were heated in concentrated hydrochloric acid to give the 4-aryl-1-
methylnaphthalenes in high yields. The same reaction was carried out in hydrochloric acid diluted with acetonitrile to give the
5,5-diaryl-4-penten-2-ones (87–96%), while treatment of the dihydrofurans with p-toluenesulfonic acid in acetonitrile afforded the
3-(2,2-diarylethenyl)-4-hydroxy-3-penten-2-ones (73–91%) which were transformed in diluted hydrochloric acid into the 5,5-diaryl-
4-penten-2-ones. It was demonstrated that the 3- and 4-penten-2-ones were intermediates of the 4-aryl-1-methylnaphthalenes since
the 3- and 4-penten-2-ones were easily converted into the corresponding naphthalenes in concentrated hydrochloric acid. The UV
irradiation of the dihydrofurans in the presence of hydrochloric acid quantitatively gave the 2-acetyl-4-aryl-1-methylnaphthalenes
(94–97%) via the same 3-penten-2-one intermediates. © 2001 Elsevier Science Ltd. All rights reserved.
In previous studies,1 we reported the convenient 3-ace-
tyl-5,5-diaryl-2-methyl-4,5-dihydrofuran synthesis using
tris(2,4-pentanedionat irradiation of the dihydrofurans
in dichloromethane gave the 2-acetyl-4-aryl-1-methyl-
naphthalenes (Scheme 1 for 1a, Table 1, entry 1).2
Highly-substituted naphthalenes are common features
of numerous biologically significant natural products
and pharmaceuticals,3 and improved methods for their
construction are highly desired.4 Although the benz-
annulation is a worthwhile synthetic method in view of
both the unique reaction mode and the practical
method providing a variety of substituted aromatic
compounds, the mechanism of the photo-induced benz-
annulation was not obvious at that time. In order to
ascertain the mechanism, we scrutinized the acid-cata-
lyzed reaction of the 3-acetyl-5,5-diaryl-2-methyl-4,5-
dihydrofurans since we knew by intuition that the
hydrogen chloride generated in situ by the photoreac-
tion of dichloromethane might promote the photo-
induced benzannulation. As a result, we could show the
optimum benzannulation conditions and the exact reac-
tion pathway by the isolation of the reaction intermedi-
ates. Herein we briefly describe the results.
Many experiments involving the photo-induced benz-
annulation of dihydrofurans 1a–d were carried out, and
O
Me
O
Me
hν
Me
O
Me
CH2Cl2, argon
(95%)
Ph
Ph
1a
5a
Scheme 1.
Keywords: acid-catalyzed transformation; dihydrofurans; pentenones; naphthalene synthesis; photocyclization.
* Corresponding author. Fax: +81-96-342-3374; e-mail: nishino@aster.sci.kumamoto-u.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00431-2

3352
S. Kajikawa et al. / Tetrahedron Letters 42 (2001) 3351–3354
Table 1. Reactions of dihydrofurans 1a–d and their products 2a, 3a, and 5aa
Entry
Substrate
Reaction conditionsb
Temp (°C)
Time (h)
Product (yield/%)c
1
2
1a
1a
UV irrad., CH2Cl2
UV irrad., 2 M
HCl–MeCN
23
23
4
3
5a (95)
5a (97)
3
4
5
1b
1c
1d
UV irrad., 2 M
HCl–MeCN
UV irrad., 2 M
HCl–MeCN
UV irrad., 2 M
HCl–MeCN
23
23
23
3
3
3
5b (96)
5c (97)
5d (47) 5d% (47)
6
7
8
9
1a
1b
1c
1d
1a
1b
1c
1d
1a
1b
1c
1d
2a
2a
3a
5a
2a
2a
2a
Conc. HCl–MeCN
Conc. HCl–MeCN
Conc. HCl–MeCN
Conc. HCl–MeCN
Conc. HCl
Conc. HCl
Conc. HCl
Conc. HCl
p-TsOH–MeCN
p-TsOH–MeCN
p-TsOH–MeCN
p-TsOH–MeCN
Conc. HCl–MeCN
Conc. HCl
Conc. HCl
Conc. HCl
UV irrad., MeCN
UV irrad., CH2Cl2
UV irrad., 2 M
HCl–MeCN
100
100
100
100
100
100
100
100
80
80
80
80
100
100
100
100
23
12
15
12
12
8
8
8
8
36
36
36
36
6
6
4
8
72
2
2a (1)
3a (94)
3b (96)
3c (87)
3d (94)
3a (4)
4c (10)
4d% (2)
4a (94)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2a (B1)
3b (93)
4c (98)
4d% (92)
2a (73)
2b (91)
2c (65)
2d (88)
3a (21)
3b (4)
3c (24)
3d (10)
3a (99)
4c (3)
4d% (B1)
4a (92)
4a (94)
No reaction
5a (87)
5a (97)
5a (98)
23
23
1.5
25
3a
UV irrad., 2 M
HCl–MeCN
23
6
Intractable
mixture
a The substrate (0.2 mmol) was stirred in solvent under an argon atmosphere (1 atm).
b Dichloromethane (10 mL), 2 M hydrochloric acid (1 mL)–acetonitrile (9 mL), concentrated hydrochloric acid (1 mL)–acetonitrile (9 mL),
concentrated hydrochloric acid (10 mL), and p-toluenesulfonic acid (2.0 mmol)–acetonitrile (10 mL) were used as the solvent system. The UV
irradiation was carried out in a 12 mL quartz cell using a 100 W high-pressure mercury lamp.
c Isolated yield based on the amount of the substrate used.
we found that the best solvent system was acetonitrile
(9 mL) containing 2 M hydrochloric acid (1 mL). The
corresponding naphthalenes 5a–d,d% were then obtained
in high yields (Scheme 2 and Table 1, entries 2–5). The
photoreaction of dihydrofuran 1d (R1=4-Cl-C6H4,
R2=4-Me-C6H4) at 23°C for 3 h gave 2-acetyl-7-
chloro-4-(4-methylphenyl)-1-mehylnaphthalene
(5d)5
and 2-acetyl-4-(4-chlorophenyl)-1,7-dimethylnaphthal-
ene (5d%)6 in the same yields. The structures of 5d and
5d% were established by spectroscopic methods and
Me
R1
R2
O H
O
O
Me
H3O+
Me
R1
O
H3O+
H3O+
R
R1
Me
R2
Ar
or
hν
O
Me
R2
Me
4a,c,d'
3a-d
2a-d
H3O+
1a-d
hν
1a-d, 2a-d, 3a-d
4a,c,d', 5a-d,d'
Me
O
1
2
a
b
c
a:
b:
c:
d:
: Ar = Ph, R = H
R = R = Ph
R
Me
1
2
: Ar = 4-Cl-C6H4, R = Cl
: Ar = 4-Me-C6H4, R = Me
: Ar = 4-Me-C6H4, R = Cl
: Ar = 4-Cl-C6H4, R = Me
R = R = 4-ClC6H4
R1 = R2 = 4-MeC6H4
R1 = 4-Cl-C6H4,
d
d'
Ar
R2 = 4-Me-C6H4
5a-d,d'
Scheme 2.

S. Kajikawa et al. / Tetrahedron Letters 42 (2001) 3351–3354
3353
Figure 1. ORTEP view of 4d% and 5d.
elemental analyses, and the structure of 5d was finally
determined by an X-ray crystallographic method (Fig.
1).5
In order to clarify the relationship of the products 2, 3,
4, and 5, the acid-catalyzed reaction of each product
was examined. The 3-penten-2-one 2a was quantita-
tively transformed into 3a in concentrated hydrochloric
acid–acetonitrile (1:9 v/v) (entry 18). The treatment of
both 2a and 3a with concentrated hydrochloric acid
resulted in the production of the deacetylated naphtha-
lene 4a (entries 19, 20). However, 2-acetylnaphthalene
5a could not be converted into 4a in hot concentrated
hydrochloric acid (entry 21). It was interesting that the
UV irradiation of 2a in 2 M hydrochloric acid–acetoni-
trile (1:9 v/v) quantitatively gave 2-acetylnaphthalene
5a and no deacetylated naphthalene 4a was detected
(entry 24). A similar UV irradiation of 3a gave only
intractable oily materials and no products were isolated
(entry 25). It was suggested that the 3-penten-2-one 2a
should be an intermediate in the photo-induced benzan-
nulation of 1a. Therefore, it was proved that the gener-
ation of hydrogen chloride was essential for the
photo-induced benzannulation of the dihydrofurans 1
in dichloromethane.2,10 In fact, stirring of 1a at 23°C
for 24 h in dichloromethane which was beforehand UV
irradiated for 4 h gave 2a (2%).
Stirring dihydrofuran 1a (R1=R2=Ph) under similar
reaction conditions without UV irradiation did not give
any products. A mixture of 1a (0.2 mmol) and concen-
trated hydrochloric acid–acetonitrile (1:9 v/v) was
heated at 100°C for 12 h, and water (30 mL) was then
added to the reaction mixture, followed by extraction
with dichloromethane (20×3 mL), giving 5,5-diphenyl-
4-penten-2-one (3a: R1=R2=Ph)7 in 94% yield along
with a small amount of 4-hydroxy-3-(2,2-diphenyl-
ethenyl)-3-penten-2-one (2a: R1=R2=Ph)8 (entry 6). A
similar reaction of 1b (R1=R2=4-Cl-C6H4) gave the
corresponding 4-penten-2-one 3b as the sole product
(entry 7). The reactions of 1c (R1=R2=4-Me-C6H4)
and 1d led to the ring-opening reaction, and the 4-
penten-2-ones 3c and 3d were produced in 87 and 94%
yield, respectively, together with small amounts of the
deacetylated naphthalenes 4c (10%) and 4d% (2%)
(entries 8 and 9). Since it was anticipated that these
reactions clearly depended on the strength of the acid,
the reaction of the dihydrofurans 1a–d was carried out
in concentrated hydrochloric acid at 100°C for 8h. As a
result, it was found that the corresponding deacetylated
naphthalenes 4a,c,d% were produced in high yields
except for the reaction of 1b which gave 3b (entries
10–13). The reaction of 1d did not give 7-chloro-4-(4-
methylphenyl)-1-methylnaphthalene (4d: Ar=4-Me-
C6H4, R=Cl), but 4-(4-chlorophenyl)-1,7-dimethyl-
naphthalene (4d%) as the sole product (entry 13). The
structure of 4d% was established by spectroscopic meth-
ods, elemental analysis, and finally by X-ray crystallog-
raphy (Fig. 1).9 On the other hand, the treatment of the
dihydrofurans 1a–d with p-toluenesulfonic acid in ace-
tonitrile afforded the 3-(2,2-diarylethenyl)-4-hydroxy-3-
penten-2-ones 2a–d in moderate to good yields (entries
14–17).
On the basis of the transformation mentioned above, it
was concluded that the UV irradiation or the presence
of acid caused the ring-opening of the 4,5-dihydro-
furans 1 to generate the 3-penten-2-one intermediates 2.
The photocyclization of the intermediates 2 accelerated
by the presence of a catalytic amount of acid produced
the 2-acetylnaphthalenes 5 (entries 22–24), whilst the
presence of a strong acid without UV irradiation pro-
moted the deacetylation of 2 to form the 4-pente-2-one
intermediates 3 which were intramolecularly cyclized to
finally give the naphthalenes 4 (Scheme 2).
The present photo-induced and/or acid-catalyzed benz-
annulation of the 4,5-dihydrofurans are very simple and
convenient, and the substituted naphthalenes as well as

3354
S. Kajikawa et al. / Tetrahedron Letters 42 (2001) 3351–3354
their intermediates can be selectively obtained in high
yields by controlling of the reaction conditions. We are
still investigating the acid-catalyzed reaction in order to
control the substituent on the naphthalene ring, and
apply it to the synthesis of ring-assembling aromatic
compounds and polycyclic aromatic hydrocarbons.
D
calcd=1.316 g/cm3; F(000)=1296.00; (vMoKa)=2.44
cm−1; 2qmax=55.0°; no. of reflections measured 21932; no.
of observations (I>3.00| (I)) 3637; no. of variables 398;
reflection/parameter ratio was 5.32; R=0.039; Rw=0.046;
GOF=1.00.
6. 2-Acetyl-4-(4-chlorophenyl)-1,7-dimethylnaphthalene (5d%):
Rf=0.50 (3:7 diethyl ether–hexane); colorless needles (from
1
hexane); mp 82.0–84.0°C; IR (CHCl3) w 1685 (CꢀO); H
NMR (300 MHz, CDCl3) l 7.98–7.24 (8H, m, arom. H),
2.79 (3H, s, CH3), 2.64 (3H, s, COCH3), 2.56 (3H, s, CH3);
13C NMR (75 MHz, CDCl3) l 204.3 (CꢀO), 138.8, 137.1,
136.8, 136.4, 133.52, 133.48, 132.5, 130.4 (arom. C), 131.3
(2C), 129.5, 128.5 (2C), 126.1, 124.8, 124.0 (arom. CH),
Acknowledgements
We thank Dr. Mikio Yasutake, Institute for Fundamen-
tal Research of Organic Chemistry, Kyushu University,
Japan, for crystallographic assistance.
31.0 (COC6 H3), 22.0, 15.9 (CH3); MS m/z (rel intensity), 308
(M+, 94), 293 (100), 265 (34), 229 (28), 215 (56); HR MS
found m/z 308.0942, calcd for C20H1735ClO M, 308.0968.
Anal. calcd for C20H17ClO: C, 77.79; H, 5.55. Found: C,
78.01; H, 5.74.
References
7. 5,5-Diphenyl-4-penten-2-one (3a): Rf=0.61 (3:7 diethyl
ether–hexane); yellow liquid; IR (CHCl3) w 1713 (CꢀO); 1H
NMR (300 MHz, CDCl3) l 7.42–7.14 (10H, m, arom. H),
6.28 (1H, t, J=7.34 Hz, CH), 3.25 (2H, d, J=7.34 Hz,
CH2), 2.12 (3H, s, COCH3); 13C NMR (75 MHz, CDCl3)
l 206.7 (CꢀO), 144.8 (>Cꢀ), 141.9, 139.5 (arom. C), 129.7
(2C), 128.4 (2C), 128.1 (2C), 127.41 (2C), 127.37 (2C)
(arom. CH), 120.5 (ꢀCH-), 44.7 (CH2), 29.9 (CH3); MS m/z
(rel intensity) 236 (14), 193 (87), 178 (29), 115 (100), 91 (53);
HR MS found m/z 236.1205, calcd for C17H16O M,
236.1201.
1. (a) Nishino, H. Bull. Chem. Soc. Jpn. 1985, 58, 1922–1927;
(b) Nishino, H.; Tategami, S.; Yamada, T.; Korp, J. D.;
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(c) Kajikawa, S.; Nishino, H.; Kurosawa, K. Heterocycles
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G.; Xie, L. J. Org. Chem. 1997, 62, 721–725; (c) Nishii, Y.;
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7195–7198; (d) Cotelle, P.; Catteau, J.-P. Tetrahedron Lett.
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787–797; (f) Kao, C.-L.; Yen, S. Y.; Chern, J.-W. Tetra-
hedron Lett. 2000, 41, 2207–2210.
8. 4-Hydroxy-3-(2,2-diphenylethenyl)-3-penten-2-one
(2a):
Rf=0.66 (3:7 diethyl ether–hexane); yellow liquid; IR
(CHCl3) w 1596 (CꢀO); 1H NMR (300 MHz, CDCl3) l
16.51 (1H, s, OH), 7.32–7.08 (10H, m, arom. H), 6.54 (1H,
s, ꢀCH-), 1.95 (6H, s, CH3×2); 13C NMR (75 MHz, CDCl3)
l 191.0 (2C) (CꢀO), 146.0 (>Cꢀ), 142.9, 140.0 (arom. C),
129.9 (2C), 128.3 (2C), 128.22 (2C), 128.18 (2C), 127.8,
127.5 (arom. CH), 122.2 (ꢀCH-), 110.6 (C-3), 24.1 (2C)
(CH3); MS m/z (rel intensity) 278 (100), 191 (44), 105 (58),
77 (42), 44 (87); HR MS found m/z 278.1300, calcd for
C19H18O2 M, 278.1307. Anal. calcd for C19H18O2: C, 81.99;
H, 6.52. Found: C, 81.93; H, 6.71.
9. 4-(4-Chlorophenyl)-1,7-dimethylnaphthalene (4d%): Rf=0.82
(3:7 diethyl ether–hexane); colorless microcrystals (from
1
hexane); mp 95.0–96.0°C; H NMR (300 MHz, CDCl3) l
7.81–7.17 (9H, m, arom. H), 2.70 (3H, s, CH3), 2.54 (3H,
s, CH3); 13C NMR (75 MHz, CDCl3) l 139.6, 137.1, 135.4,
133.5, 133.01, 132.96, 129.6 (arom. C), 131.4 (2C), 128.4
(2C), 128.0, 126.2, 126.1, 125.7, 123.6 (arom. CH), 21.9,
19.6 (CH3); MS m/z (rel intensity) 266 (100), 228 (22), 215
(31), 196 (41). Anal. calcd for C18H15Cl: C, 81.04; H, 5.67.
Found: C, 81.23; H, 5.91. X-ray crystallographic data of
4d% (Ar=4-Cl-C6H4, R=Me): empirical formula C18H15Cl;
formula weight 266.77; colorless platelet; crystal dimen-
sions 0.05×0.35×0.10 mm; orthorhombic; space group
5. 2-Acetyl-7-chloro-4-(4-methylphenyl)-1-methylnaphthalene
(5d): Rf=0.54 (3:7 diethyl ether–hexane); light yellow
microcrystals (from methanol); mp 61.5–63.0°C; IR
(CHCl3) w 1688 (CꢀO); 1H NMR (300 MHz, CDCl3) l
8.16–7.23 (8H, m, arom. H), 2.75 (3H, s, CH3), 2.63 (3H,
s, COCH3), 2.45 (3H, s, CH3); 13C NMR (75 MHz, CDCl3)
l 204.1 (CꢀO), 138.7, 137.7, 137.6, 136.7, 134.2, 132.7,
131.6, 130.8 (arom. C), 129.8 (2C), 128.2 (2C), 128.5, 127.7,
124.9, 124.5 (arom. CH), 30.9 (COC6 H3), 21.2, 15.7 (CH3);
,
Fdd2 (no. 43); a=19.702(2), b=51.114(3), c=5.3845(3) A,
MS m/z (rel intensity), 308 (M+, 96), 293 (100), 265 (48),
229 (32), 215 (60); HR MS found m/z 308.1015, calcd for
C20H1735ClO M, 308.0968. Anal. calcd for C20H17ClO: C,
77.79; H, 5.55. Found: C, 78.04; H, 5.68. X-ray crystallo-
graphic data of 5d (Ar=4-Me-C6H4, R=Cl): empirical
formula C20H17ClO; formula weight 308.81; colorless
prism; crystal dimensions 0.20×0.05×0.50 mm; orthorhom-
3
V=5422.5(6) A , Z=16; Dcalcd=1.307 g/cm3; F(000)=
,
2240.00; (vMoKa)=2.63 cm−1; 2qmax=55.0°; no. of reflec-
tions measured 10424; no. of observations (I>3.00| (I))
1450; no. of variables 285; reflection/parameter ratio was
5.09; R=0.035; Rw=0.043; GOF=1.18.
10. (a) Ohkura, K.; Noguchi, Y.; Seki, K. Chem. Lett. 1997,
99–100; (b) Matohara, K.; Lim, C.; Yasutake, M.; Nogita,
R.; Koga, T.; Sakamoto, Y.; Shinmyozu, T. Tetrahedron
Lett. 2000, 41, 6803–6807.
bic; space group Pna21 (no. 33); a=22.9004(8), b=
3
,
,
6.0532(2), c=22.4819(6) A, V=3116.5(5) A , Z=8;