Convenient one-pot method for the preparation of polysubstituted benzo[b]- and naphtho[1,2-b]-furans and -thiophenes

Article abstract of DOI:10.1039/a708809d

N-(Phenoxymethyl)- and N-(phenylthiomethyl)-benzotriazoles are versatile substrates for the preparation of benzofurans and benzothiophenes by insertion reactions of their anions into alkyl and aryl aldehydes and in situ cyclization of the α-aryloxy and α-arylthio ketones thus formed. N-(Naphthyloxy)- and N-(naphthylthio)-benzotriazoles are similarly efficient precursors for naphthofurans and naphthothiophenes.

Full text of DOI:10.1039/a708809d

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Convenient one-pot method for the preparation of polysubstituted
benzo[b]- and naphtho[1,2-b]-furans and -thiophenes
Alan R. Katritzky,* Larisa Serdyuk and Linghong Xie
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, FL 32611-7200, USA
N-(Phenoxymethyl)- and N-(phenylthiomethyl)-benzotriazoles are versatile substrates for the preparation
of benzofurans and benzothiophenes by insertion reactions of their anions into alkyl and aryl aldehydes
and in situ cyclization of the á-aryloxy and á-arylthio ketones thus formed. N-(Naphthyloxy)- and
N-(naphthylthio)-benzotriazoles are similarly efficient precursors for naphthofurans and
naphthothiophenes.
have now extended this methodology to provide convenient
one-pot procedures to prepare polysubstituted benzo[b]furans
and benzo[b]thiophenes.
Introduction
The constant and growing interest in the development of new
efficient and general synthetic methods for the preparation of
fused heterocyclic systems involving furan and thiophene sub-
units is justified by their well-established valuable physiological
and pharmacological properties.1–4 In addition, recent technical
applications of polysubstituted benzofurans and benzothio-
phenes, including numerous fluorescent dyes used as retrograde
tracers, and Ca2ϩ and Mg2ϩ fluorescent indicator conjugates,
etc.4,5 increase their significance.
Results and discussion
1-(Aryloxymethyl)benzotriazoles 3a–c were prepared by reac-
tions of 1-chloromethylbenzotriazole 1 with polysubstituted
phenols 2a–c (Scheme 2). Lithiation of phenyl ethers 3a–c with
BunLi, followed by quenching with an appropriate electro-
phile, afforded the substituted benzotriazole derivatives 4a–f.
Alkyl intermediates 4 could be isolated, and this was done for
the cases of 4a and 4b. In general, 4a–f were used directly in the
next step. Treatment of 4a–f with an additional equivalent of
BunLi, and subsequently with an aldehyde formed intermedi-
ates 5a–f. Once again, derivatives 5 could be isolated and char-
acterized, and this was done in the case of 5b. However, in
general, 5a–f were treated directly without isolation with ZnBr2
(neat mixture of 140 ЊC), to afford the corresponding α-aryloxy
ketones 6a–f as a result of pinacol-type rearrangement (cf. ref.
14). Here also, 6a–f were generally not isolated; the resulting
mixture was heated at 175–180 ЊC for 10–24 h, to give the
desired polysubstituted benzo[b]furans 7a–f in good overall
yields (49–80% for four steps). Several α-aryloxy ketones 6a–e
were isolated in the course of the reactions in order to prove the
reaction sequence; on further treatment with ZnBr2 at elevated
temperature, 6a–e each gave the corresponding benzofuran
7a–e, respectively.
Following a similar protocol, various substituted benzo[b]-
thiophenes 7g and 7h (Scheme 2) were prepared in one-pot
procedures from 1-(arylthiomethyl)benzotriazoles 3d and 3e
via the corresponding alkylated analogs 4, and arylthio ketones
6. Just as for the sequence leading to the analogous benzo-
furans, intermediates (4h and 6h) were isolated during the
course of these similar transformations in the benzo[b]-
thiophene series. Cyclization of ketones 6g and 6h occurred
smoothly in hot (120–125 ЊC) polyphosphoric acid, leading to
the expected benzo[b]thiophenes 7g and 7h in good overall
yields (75–78%). Polyphosphoric acid is the reagent/solvent of
choice for the benzo[b]thiophene series: when the ketone 6h
was treated with zinc bromide at elevated temperature under
conditions similar to the preparation of the benzo[b]furan
series, only a low yield (ca. 5%, according to the GC–MS data)
of the desired product 7h was obtained after 40 h of heating;
instead, di-p-tolyl disulfide (15%) and 1,4-di-p-toluoylbutane
(35%) were isolated from the reaction mixture by column
chromatography together with unreacted starting ketone
6h. This may be explained by the thermal instability of ketones
6g, 6h derived from thiophenol: the structures of the by-
products clearly indicate a radical cleavage of the tert-C᎐S
bond. The linear structure of 1,4-di-p-toluoylbutane was formed
Benzo[b]furans A and benzo[b]thiophenes C (Scheme 1) are
R2
R2
O
R2
R1
R1
R
R1
R
R
O
S
X
X = O, S
B
A
C
Scheme 1
each available by two general routes: (i) the construction of a
fused benzene ring starting from 2-substituted furans6a or
thiophenes,6b–d and (ii) the formation of a furan6e–l or thio-
phene6l–n moiety beginning with S(O)-substituted derivatives of
(thio)phenols. The extensive literature devoted to such methods
has been summarized.1,7–9
Among the known methods, both benzo[b]furans A and
benzo[b]thiophenes C have most frequently been obtained by
acid-catalyzed cyclizations of α-substituted aryl(thio)oxycar-
bonyl compounds of general type B,1,9 a route which has proven
to be of great value for the synthesis of a wide variety of A and
C. The assembling of a benzene ring from derivatized furans or
thiophenes has been of lesser synthetic importance (annulation
of a benzene ring;2 the scope and limitations of this method for
the benzothiophene series were recently given6d). Aryl(thio)oxy
keto-derivatives of type B are often prepared by means of con-
densation of (thio)phenols and α-halogeno-β-keto esters in the
presence of bases (for an example, see ref. 10). The analogous
α-aryl(thio)oxy aldehydes are frequently used in a protected
(acetal) form, and are prepared from (thio)phenols and α-halo
acetals.11–13 Known methods for the preparation of both benzo-
[b]furans and benzo[b]thiophenes are briefly compared later
in this paper, but no existing method is completely general. The
preparations of aryl(thio)oxy ketones of type B also possess
certain limitations, especially as far as varieties of R1 and R2
substituent are concerned. Hence, novel general routes for
both benzo[b]furans and benzo[b]thiophenes retain synthetic
importance.
We recently developed an efficient method for carbon inser-
tion, which allowed the preparation of several new α-aryl-
(thio)oxy ketones in moderate to good yields (53–86%).14 We
J. Chem. Soc., Perkin Trans. 1, 1998
1059

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Zn(OH)Br2
R3
R3
–
R2
R1
O
X
R2
R1
Bt
+
NaOH
DMF
ZnBr2
R4
XH
R4
X
BtCH2Cl +
R
R
X
1
R5
R6
R5
3a–e
R6
8
6
2a–e
2,3
X
R3 R4
R5
R6
∆
N
Zn(OH)Br2
–
a
b
c
d
e
O
O
O
S
H
H
H
H
H
H
H
N
Bt =
i) BunLi–THF
ii) R1Hlg
C
2H5
R2
N
CH3 CH3 CH3
H
H
H
H
H
R
R2
+
X
Cl
CH3
H
H
R1
R
S
X
R3
Bt R1 OH
R2
R3
R1
Bt
X
R1
9
7
THF
R4
X
H
R4
i) BunLi
ii) R2CHO
Zn(OH)Br2
–
R5
R6
5a–e
ZnBr2
R5
R6
R1
R1
R2
4a–e
+
∆
R2
R
R
neat, 140 °C
X
X
R2
7′
10
R3
R2
R3
O
Scheme 3
X = O: ZnBr2/175–180 °C
X = S: PPA/120–125 °C
R4
R5
R1
on the lability of the X᎐C᎐R2 and X᎐C᎐R1 bonds, either 10, or
8 can be formed, and thus variously substituted benzofurans or
benzothiophenes can result (Scheme 3).
R1
R4
X
X
R5
R6
R6
Naphthofurans 16a and 16b and naphthothiophenes 16c and
16d with various substituents at the C(2) and C(3) positions
were prepared (Scheme 4) in overall yields of 71–83%, by a
route similar to that for the benzo-furan and -thiophene series
described above. The (benzotriazol-1-yl)methyl 1-naphthyl
(thio)ethers 12a and 12b were isolated (95% yield in both cases),
but all the subsequent transformations were performed in one-
pot sequences: lithiation and addition of alkyl halide afforded
substituted (thio)naphthols 13a–d, which were treated in situ
6a–e
7a–h
4–7
X
R1
R2
R3 R4
R5
R6
a
b
c
d
e
f
O
O
O
O
O
O
S
C6H5CH2 C6H5(CH2)2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
n-C8H17
CH3
4-CH3C6H4
4-CH3C6H4
2,4-Cl2C6H3
C6H5
H
H
n-C4H9
n-C3H7
n-C6H13
H
C2H5
H
4-ClC6H4
CH3 CH3 CH3
g
h
C6H5CH2 C6H5(CH2)2
CH3 4-CH3C6H4
H
H
Cl
H
H
H
XH
X
Bt
S
CH3
H
Scheme 2
NaOH
DMF
BtCH2Cl
+
via migration of the unpaired electron to the methyl carbon
atom followed by the recombination of two radical species.
Cyclization of ketones of general type 6 (Scheme 3) is con-
sidered to be the best way to prepare symmetrical 2,3-
dialkylsubstituted benzo[b]furans and benzo[b]thiophenes.1
When the corresponding unsymmetrically substituted ketones
(R1 ≠ R2 ≠ H) are employed, mixtures of regioisomers with sub-
stituents partly exchanged at the C(2) and C(3) positions were
usually obtained.1,15 The isomer ratio has been shown to
depend greatly on the reaction temperature in the benzofuran
series, and, accordingly, in order to obtain benzofurans or ben-
zothiophenes free from the corresponding regioisomers, special
reagents/methods need to be used.1 In our reactions involving
the use of both zinc bromide and polyphosphoric acid, the for-
mation of alternative isomers was largely suppressed, leading to
predominant isolation of products 7a–h with the expected
1
12a,b
11a,b
11, 12a: X = O
11, 12b: X = S
i) BunLi–THF
ii) R1Hlg
R2
Bt
R1
Bt
HO
H
X
R1
THF
X
i) BunLi
ii) R2CHO
14a–d
ZnBr2
13a–d
neat, 140 °C
R2
R2
1
O
unrearranged structure. However, in the H NMR spectra of
16a: ZnBr2/175–180 °C
16b–d: PPA/120–125 °C
R1
some products, i.e. 7a, a second weak set of signals for the
corresponding positional isomer was observed. The GC–MS
spectra of initially isolated 7a and 7b also show existence of a
second peak of the same molecular weight, but with different
fragmentation. The ratio of ‘regular’ 7 and ‘reversed’ 7Ј prod-
ucts, according to the GC–MS data, was ca. 13:1 in the case of
7a and 20:1 in the case of 7b. Cyclodehydration reactions lead-
ing to the formation of benzofurans and benzothiophenes with
substituents swapped at the C(2) and C(3) positions, probably,
involve cations of type 8, which exist in equilibrium with the
corresponding 3-membered heterocyclic cations 9: depending
R1
X
X
15a–d
16a–d
X
O
O
S
R1
R2
13–16
C6H5(CH2)3 4-ClC6H4
a
b
c
n-C4H9
C6H5CH2
n-C3H7
C6H5(CH2)2
4-ClC6H4
C6H5(CH2)2
d
S
Scheme 4
1060
J. Chem. Soc., Perkin Trans. 1, 1998

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with more BunLi and various aldehydes to form the appropri-
ate alcohols 14a–d. The Lewis acid (ZnBr2) induced carbon
insertion and formed the corresponding ketones 15a–d. For the
preparation of naphthofuran 16a the temperature was raised to
175–180 ЊC, while for the preparation of 16b and naphthothio-
phenes 16c and 16d polyphosphoric acid was added, followed
by an increase in temperature to 120–125 ЊC. The high tempera-
ture (neat) cyclization of the intermediate 15b gave a mixture of
desired benzophenone 16b and a by-product whose structure
appears to include a naphthopyran ring (according to NMR
spectra of the crude reaction mixture). However, all attempts to
separate 16b and the by-product failed. Therefore we used PPA-
catalyzed cyclization for the preparation of 16b. The reactions
were monitored by TLC and GC–MS of the reaction mixtures;
after they were complete, simple work-up afforded the desired
naphthofurans 16a and 16b and naphthothiophenes 16c and
16d. As in the benzothiophene preparations, the use of ZnBr2
for cyclization of naphthothio ketone 15c after 20 h of heating
at 175–180 ЊC did not give a substantial amount of 16c, but led
instead to the formation of di(1-naphthyl) disulfide (15%) and
1,4-bis(4-chlorobenzoyl)-2,3-diphenylbutane (16%). As in the
case of 6h, the last named product was a result of consecutive
rearrangement–recombination of the radical formed after
thermal decomposition of ketone 15c. Intermediates 13 and 15
could be isolated, as we demonstrated for the cases of 13a and
15a, 15b and 15d, and then could be converted smoothly into
the corresponding naphtho-furans and -thiophenes 16, as
shown for the cases of 15a and 15d (see Experimental), which
increases the synthetic utility of the new process.
65–70 ЊC for 15 h. On cooling, the mixture was poured into ice–
water to give crystals, which were filtered, washed with water
(100 cm3) and dried to afford the pure products 3a–e and 12a,b.
1-(Phenoxymethyl)benzotriazole 3a. Isolated as a white solid
(3.24 g, 96%), mp 64–65 ЊC (lit.,16 64 ЊC); δH(300 MHz; CDCl3)
6.56 (2 H, s), 7.03 (1 H, t, J 7.2), 7.09 (2 H, d, J 8.2), 7.28 (2 H,
d, J 7.2), 7.41 (1 H, t, J 8.0), 7.53 (1 H, t, J 8.0), 7.70 (1 H, d, J
8.3), 8.08 (1 H, d, J 8.31); δC(75 MHz; CDCl3) 75.0, 109.9,
116.4, 120.1, 123.1, 124.4, 128.1, 129.7, 132.8, 146.3 and 156.2.
1-(2-Ethylphenoxymethyl)benzotriazole 3b. Isolated as a white
solid (2.88 g, 76%), mp 54–55 ЊC (Found: N, 16.76. Calc. for
C15H15N3O: N, 16.60%); δH(300 MHz; CDCl3) 1.10 (3 H, t, J
7.4), 2.54 (2 H, q, J 7.4), 6.59 (2 H, s), 6.96–7.01 (1 H, m), 7.14–
7.19 (3 H, m), 7.42 (1 H, t, J 7.5), 7.54 (1 H, t, J 7.5), 7.66 (1 H,
d, J 8.2), 8.09 (1 H, d, J 8.2); δC(75 MHz; CDCl3) 14.2, 22.9,
75.0, 109.7, 114.0, 120.0, 123.0, 124.3, 127.0, 128.0, 129.5,
132.8, 133.9, 146.2 and 154.0.
1-(3,4,5-Trimethylphenoxymethylbenzotriazole 3c. Isolated as
a white solid (3.65 g, 91%), mp 98–99 ЊC (Found: C, 71.86; H,
6.75; N, 16.10. Calc. for C16H17N3O: C, 71.99; H, 6.41; N,
15.72%); δH(300 MHz; CDCl3) 2.07 (3 H, s), 2.21 (6 H, s), 6.50
(2 H, s), 6.73 (2 H, s), 7.40 (1 H, t, J 7.5), 7.53 (1 H, t, J 7.5),
7.70 (1 H, d, J 8.2), 8.07 (1 H, d, J 8.2); δC(75 MHz; CDCl3)
14.6, 20.7, 75.3, 110.0, 115.4, 120.1, 124.4, 128.0, 129.8, 132.9,
137.9, 146.4 and 153.6.
1-[(4-Chlorophenyl)thiomethyl]benzotriazole 3d. Isolated as a
white solid (4.00 g, 97%), mp 105–106 ЊC (Found: C, 56.72; H,
3.57; N, 15.33. Calc. for C13H10N3ClS: C, 56.72; H, 3.66; N,
15.27%); δH(300 MHz; CDCl3) 5.93 (2 H, s), 7.16–7.23 (4 H, m),
7.38–7.51 (3 H, m), 8.07 (1 H, d, J 8.2); δC(75 MHz; CDCl3)
52.6, 110.0, 120.3, 124.3, 127.6, 129.5, 130.3, 132.1, 134.4, 135.3
and 146.5.
Conclusion
One-carbon homologation reaction of benzotriazole-con-
taining (thio)alkoxy derivatives 4, 13 afforded a new series of
α-(thio)alkoxy-substituted ketones 6a–h and 15a–d, which were
subsequently cyclized to give a wide range of various substi-
tuted benzo[b]furans 7a–f and benzo[b]thiophenes 7g,h. Several
compounds, fused benzo derivatives, were also prepared, i.e.
naphtho[1,2-b]furans 16a,b and naphtho[1,2-b]thiophenes
16c,d. The overall yields of compounds 7a–h were in the range
of 49–80%, while 16a–d yields were 71–83%. The reaction
sequence was performed in a one-pot manner, starting from the
corresponding (benzotriazol-1-yl)methyl aryl (thio)ethers 3a–e
and 12a,b. The procedure is simple, efficient, and more general
than most of the previously used methods, thus adding a valu-
able alternative to the known reactions for the preparation of
benzo[b]furans and benzo[b]thiophenes.
1-[(4-Methylphenyl)thiomethyl]benzotriazole 3e. Isolated as a
white solid (3.56 g, 93%), mp 104–105 ЊC (Found: N, 16.91. Calc.
for C14H13N3S: N, 16.47%); δH(300 MHz; CDCl3) 2.30 (3 H, s),
5.89 (2 H, s), 7.03 (2 H, d, J 8.0), 7.12 (2 H, d, J 8.0), 7.35–7.46 (3
H, m), 8.08 (1 H, d, J 8.3); δC(75 MHz; CDCl3) 21.1, 53.2, 110.2,
120.1, 124.1, 127.3, 128.2, 130.1, 132.2, 133.5, 139.1 and 146.4.
1-(1-Naphthyloxymethyl)benzotriazole 12a. Isolated as a white
solid (3.92 g, 95%), mp 102–103 ЊC (Found: C, 74.11; H, 4.76;
N, 15.36. Calc. for C17H13N3O: C, 74.17; H, 4.76; N, 15.26%);
δH(300 MHz; CDCl3) 6.65 (2 H, s), 7.16 (1 H, d, J 7.5), 7.31 (2
H, t, J 8.0), 7.37–7.48 (4 H, m), 7.63 (1 H, d, J 8.0), 7.74 (1 H, d,
J 7.4), 8.03 (1 H, d, J 8.2), 8.11 (1 H, d, J 8.5); δC(75 MHz;
CDCl3) 74.8, 108.0, 109.6, 119.9, 121.3, 122.6, 124.3, 125.4,
125.6, 125.7, 126.5, 127.5, 128.1, 132.7, 134.5, 146.2 and 151.7.
1-(1-Naphthylthiomethyl)benzotriazole 12b. Isolated as white
crystals (4.15 g, 95%), mp 103–104 ЊC (Found: C, 69.76; H,
4.57; N, 14.29. Calc. for C17H13N3S: C, 70.08; H, 4.50; N,
14.42%); δH(300 MHz; CDCl3) 6.01 (2 H, s), 7.30–7.46 (6 H, m),
7.61–7.78 (4 H, m), 8.02 (1 H, d, J 7.6); δC(75 MHz; CDCl3)
52.6, 110.1, 120.1, 124.1, 126.7, 126.8, 127.4, 127.6, 127.7,
129.1, 129.2, 129.3, 132.2, 132.4, 132.9, 133.5 and 146.4.
Experimental
General
Melting points were determined with a hot-stage apparatus and
are uncorrected. NMR spectra were taken in CDCl3 with
tetramethylsilane as the internal standard for 1H (300 MHz) or
solvent as the internal standard for 13C (75 MHz). J Values are
given in Hz. Tetrahydrofuran (THF) was distilled under nitro-
gen immediately prior to use from sodium–benzophenone. All
reactions with air-sensitive compounds were carried out under
an argon atmosphere. Column chromatography was conducted
with silica gel 230–400 mesh.
General procedure for the preparation of 1-(benzotriazol-1-yl)-1-
phenoxy 1-substituted methanes 4a,b, 1-(benzotriazol-1-yl)-1-(4-
methylphenylthio)ethane 4h, and 1-(1-naphthyloxy)-1-
(benzotriazol-1-yl)-4-phenylbutane 13a
To a stirred solution of the corresponding 1-(aryloxymethyl)-
benzotriazoles 3a,b, 1-[(4-methylphenyl)thiomethyl]benzo-
triazole 3e, or 1-(1-naphthyloxymethyl)benzotriazole 12a (5
mmol) in dry THF (50 cm3) at Ϫ78 ЊC under argon BunLi
(1.6 , 3.8 cm3, 5.5 mmol) was added. After 1 h, the appropriate
electrophile (5.5 mmol) [benzyl bromide (0.94 g) for 4a, n-octyl
iodide (1.32 g) for 4b, methyl iodide (0.78 g) for 4h, or 1-phenyl-
3-bromopropane (1.00 g) for 13a] in THF (5 cm3) was added.
The mixture was stirred at Ϫ78 ЊC for an additional 3 h and
then at room temperature overnight. After being quenched with
water (50 cm3), the mixture was extracted with Et2O (3 × 50
cm3) and the combined organic layer was dried (Na2SO4). The
General procedure for the preparation of 1-(aryloxymethyl)-
benzotriazoles 3a–c, 1-(arylthiomethyl)benzotriazoles 3d and
3e, 1-(1-naphthyloxymethyl)benzotriazole 12a, and
1-(1-naphthylthiomethyl)benzotriazole 12b
To a stirred solution of the corresponding (thio)phenol 2a–e or
(thio)naphthol 11a,b (15 mmol) in ethanol (50 cm3), NaOH
(15 mmol, 0.60 g) was added at room temperature. After 1 h,
ethanol was evaporated in vacuo, and a solution of 1-chloro-
methylbenzotriazole 1 (15 mmol, 2.51 g) in DMF (50 cm3) was
added to the resulting solid. The reaction mixture was heated at
J. Chem. Soc., Perkin Trans. 1, 1998
1061

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solvent was evaporated in vacuo and the residue purified either
by recrystallization or by column chromatography to give the
corresponding pure product 4a, 4b, 4h or 13a.
General procedure for the preparation of á-aryl(thio)oxy ketones
6a–e, 6h and á-naphthyl(thio)oxy ketones 15a, 15b and 15d
To stirred solution of the corresponding 1-(aryloxy-
a
1-(Benzotriazol-1-yl)-1-phenoxy-2-phenylethane 4a. Purified
by recrystallization from CH2Cl2–hexane to give a white solid
(1.50 g, 95%), mp 89–90 ЊC (Found: C, 76.17; H, 5.47; N, 13.56.
Calc. for C20H17N3O: C, 76.17; H, 5.43; N, 13.32%); δH(300
MHz; CDCl3) 3.55 (1 H, dd, J 6.0, 14.0), 3.79 (1 H, dd, J 6.0,
14.0), 6.85–7.00 (4 H, m), 7.09–7.17 (3 H, m), 7.19–7.23 (2 H,
m), 7.32 (1 H, t, J 8.0), 7.43 (1 H, t, J 8.0), 7.76 (1 H, d, J 8.3),
8.01 (1 H, d, J 8.3); δC(75 MHz; CDCl3) 41.4, 89.0, 111.0, 116.4,
120.2, 123.1, 124.2, 127.4, 127.7, 128.6, 129.4, 129.6, 131.7,
134.5, 146.6 and 156.1.
1-(Benzotriazol-1-yl)-1-phenoxynonane 4b. Purified by col-
umn chromatography (hexane–EtOAc = 8:1) to give a colour-
less oil (1.48 g, 88%) (Found: C, 74.98; H, 8.46; N, 12.41. Calc.
for C21H27N3O: C, 74.74; H, 8.06; N, 12.45%); δH(300 MHz;
CDCl3) 0.87 (3 H, t, J 6.5), 1.13–1.61 (12 H, m), 2.25–2.40 (1 H,
m), 2.43–2.58 (1 H, m), 6.84–6.93 (2 H, m), 6.98 (2 H, d, J 7.9),
7.15 (2 H, t, J 7.9), 7.30 (1 H, t, J 7.6), 7.42 (1 H, t, J 7.6), 7.82
(1 H, d, J 8.4), 8.02 (1 H, d, J 8.4); δC(75 MHz; CDCl3) 13.8,
22.4, 24.5, 28.7, 28.8, 29.0, 31.5, 34.6, 88.2, 111.0, 116.1, 119.9,
122.7, 124.0, 127.4, 129.4, 131.0, 146.6 and 156.1.
1-(Benzotriazol-1-yl)-1-(4-methylphenylthio)ethane 4h. Puri-
fied by column chromatography (hexane–EtOAc = 8:1) to give
a colourless oil (1.21 g, 90%) (Found: C, 66.75; H, 5.98; N,
15.74. Calc. for C15H15N3S: C, 66.89; H, 5.62; N, 15.61%);
δH(300 MHz; CDCl3) 2.09 (3 H, d, J 7.1), 2.22 (3 H, s), 6.25 (1
H, q, J 7.1), 6.88–6.95 (4 H, m), 7.35 (1 H, t, J 7.3), 7.44 (1 H, t,
J 7.3), 7.68 (1 H, d, J 8.3), 8.03 (1 H, d, J 8.3); δC(75 MHz;
CDCl3) 20.6, 21.0, 63.1, 111.1, 120.0, 123.8, 126.9, 127.2, 129.7,
131.4, 134.2, 139.2 and 146.5.
1-(1-Naphthyloxy)-1-(benzotriazol-1-yl)-4-phenylbutane 13a.
Purified by column chromatography (hexane–EtOAc = 8:1) to
give a colourless oil (1.75 g, 89%); m/z (FAB) 394.1913 (M ϩ 1).
C26H23N3O requires 394.1919; δH(300 MHz; CDCl3) 1.60–1.75
(1 H, m), 1.88–2.03 (1 H, m), 2.42–2.54 (1 H, m), 2.60–2.79 (3
H, m), 6.91 (1 H, d, J 7.7), 7.03–7.52 (12 H, m), 7.72 (2 H, d, J
8.0), 8.01 (1 H, d, J 8.2), 8.31 (1 H, d, J 8.0); δC(75 MHz;
CDCl3) 26.2, 34.2, 34.9, 87.7, 107.7, 111.0, 120.1, 121.3, 122.4,
124.3, 125.5, 125.6, 125.7, 126.0, 126.5, 127.7, 127.8, 128.3,
128.4, 131.1, 134.5, 141.0, 146.6 and 151.6.
methyl)benzotriazoles 3a,c, 1-[(4-methylphenyl)thiomethyl]-
benzotriazole 3e, 1-(1-naphthyloxymethyl)benzotriazole 12a, or
1-(1-naphthylthiomethyl)benzotriazole 12b (5 mmol) in dry
THF (50 cm3) at Ϫ78 ЊC under argon, BunLi (1.6 , 3.8 cm3,
5.5 mmol) was added. After 1 h, the appropriate electrophile
(5.5 mmol) [benzyl bromide (0.94 g) for 6a, n-octyl iodide (1.32
g) for 6b, methyl iodide (0.78 g) for 6c and 6h, n-butyl bromide
(0.75 g) for 6d and 15b, 1-phenyl-3-bromopropane (1.00 g) for
15a, or n-propyl iodide (0.93 g) for 6e and 15d] in THF (5 cm3)
was added. The mixture was stirred at Ϫ78 ЊC for an additional
3 h and then at room temperature overnight. The solution
formed was cooled again to Ϫ78 ЊC, and another equivalent of
BunLi (1.6 , 3.8 cm3, 5.5 mmol) was added. After 2 min, the
appropriate aldehyde (5.5 mmol) [hydrocinnamaldehyde (0.74
g) for 6a, 15b and 15d, 4-methylbenzaldehyde (0.66 g) for 6b, 6c
and 6h, 2,4-dichlorobenzaldehyde (0.96 g) for 6d, benzaldehyde
(0.58 g) for 6e, or 4-chlorobenzaldehyde (0.77 g) for 15a], in
THF (5 cm3) was added. The mixture was stirred at Ϫ78 ЊC for
an additional 3 h and then at room temperature overnight. A
solution of ZnBr2 (12 mmol, 2.7 g) in THF (10 cm3) was added,
the solvent was distilled off, and the oily residue was heated at
140 ЊC for 10 h. Upon cooling, crude product was dissolved in
Et2O, filtered, quenched with water (50 cm3) and extracted with
Et2O (3 × 50 cm3). The combined organic layer was dried
(Na2SO4). The solvent was evaporated in vacuo and the residue
purified by column chromatography to give the corresponding
pure products 6 or 15.
1,5-Diphenyl-2-phenoxypentan-3-one 6a. Purified by column
chromatography (hexane–EtOAc = 20:1) to give a colourless
oil (1.02 g, 62%) (Found: C, 83.61; H, 6.64. Calc. for C23H22O2:
C, 83.60; H, 6.71%); δH(300 MHz, CDCl3) 2.66–2.82 (4 H, m),
3.09 (2 H, d, J 6.2), 4.73 (1 H, t, J 6.2), 6.76 (2 H, d, J 8.2), 6.94
(1 H, t, J 7.5), 7.05 (2 H, d, J 7.7), 7.13–7.31 (10 H, m); δC(75
MHz; CDCl3) 28.9, 38.4, 39.9, 83.7, 115.0, 121.6, 126.0, 126.8,
128.3, 129.5, 129.7, 136.2, 140.8 157.6 and 210.7.
1-(4-Methylphenyl)-2-phenoxydecan-1-one 6b. Purified by
column chromatography (hexane–EtOAc = 40:1) to give a
colourless oil (1.28 g, 76%) (Found: C, 81.31; H, 9.21.
Calc. for C23H30O2: C, 81.60; H, 8.94%); δH(300 MHz, CDCl3)
0.87 (3 H, t, J 4.7), 1.20–1.41 (10 H, m), 1.42–1.71 (2 H, m),
1.84–2.21 (2 H, m), 2.36 (3 H, s), 5.26 (1 H, dd, J 4.7, 8.1), 6.82–
6.91 (3 H, m), 7.14–7.25 (4 H, m), 7.99 (2 H, d, J 8.3); δC(75
MHz; CDCl3) 14.0, 21.5, 22.5, 25.7, 29.1, 29.2, 29.3, 31.7, 33.4,
81.3, 115.1, 121.1, 128.8, 129.3, 129.4, 131.9, 144.3, 157.9 and
198.5.
Preparation of 1-(4-methylphenyl)-2-(benzotriazol-1-yl)-2-
phenoxydecanol 5b
To a stirred solution of 4b (5 mmol) in dry THF (50 cm3) at
Ϫ78 ЊC under argon BunLi (1.6 , 3.8 cm3, 5.5 mmol) was
added. After 2 min, 4-methylbenzaldehyde (5.5 mmol, 0.66 g)
in THF (5 cm3) was added. The mixture was stirred at Ϫ78 ЊC
for an additional 3 h and then at room temperature overnight.
After being quenched with water (50 cm3), the mixture was
extracted with Et2O (3 × 50 cm3) and the combined organic
layer was dried (Na2SO4). The solvent was evaporated in vacuo
and the residue purified by column chromatography (hexane–
EtOAc = 8:1) to give product 5b as a mixture of diastereomers;
a colourless oil (1.26 g, isolated yield 55%) (Found: N, 9.39.
Calc. for C29H35N3O2: N, 9.18%); δH(300 MHz; CDCl3) (data
in square brackets are given for minor isomer, the ratio of
the products, according to the GC–MS data, is 2:1) 0.85 (3 H, t,
J 5.3), 0.98–1.26 (10 H, m), 1.42–1.54 (2 H, m), 2.26 (3 H, s)
[2.20 (3 H, s)], 2.62–2.69 (2 H, m), 3.62 (1 H, br s), [3.42 (1 H,
br s)], 5.57 (1 H, s), [5.43 (1 H, s)], 6.51–6.55 (2 H, m), 6.72
(2 H, d, J 8.1) [6.65 (2 H, d, J 8.1)], [6.84 (2 H, d, J 7.8)],
6.91–6.97 (2 H, m), 7.02–7.11 (3 H, m), 7.27–7.30 (2 H, m),
7.87–7.90 (1 H, m), 7.97–8.03 (1 H, m); δC(75 MHz; CDCl3)
14.0, 21.1 [20.9], 22.5 [22.4], 22.9, 28.8, 28.9, 29.4, 31.6, 32.8,
78.1 [77.3], 98.98 [99.0], 114.5 [113.3], 119.1 [119.2], 119.4
[119.3], 123.2 [123.4], 123.9 [123.7], 127.1 [127.06], 127.4, 128.6
[128.4], 129.4 [129.3], 134.1 [134.0], 134.2, 138.3 [138.2], 146.0
[145.9] and 153.9 [153.8].
1-(4-Methylphenyl)-2-phenoxypropan-1-one 6c. Purified by
column chromatography (hexane–EtOAc = 8:1) to give white
crystals (1.00 g, 84%), mp 74–75 ЊC (Found: C, 80.21; H, 6.96.
Calc. for C16H16O2: C, 79.97; H, 6.71%); δH(300 MHz; CDCl3)
1.68 (3 H, d, J 6.8), 2.37 (3 H, s), 5.45 (1 H, q, J 6.8), 6.83–6.93
(3 H, m), 7.17–7.26 (4 H, m), 7.98 (2 H, d, J 8.3); δC(75 MHz;
CDCl3) 18.7, 21.6, 76.5, 115.1, 121.3, 128.9, 129.4, 129.5, 131.6,
144.5, 157.4 and 198.4.
1-(2,4-Dichlorophenyl)-2-phenoxyhexan-1-one 6d. Purified by
column chromatography (hexane–EtOAc = 8:1) to give a
colourless oil (1.10 g, 66%) (Found: C, 63.89; H, 5.55. Calc.
for C18H18Cl2O2: C, 64.11; H, 5.38%); δH(300 MHz; CDCl3)
0.89 (3 H, t, J 7.2), 1.25–1.42 (2 H, m), 1.45–1.61 (2 H, m),
1.92–1.99 (2 H, m), 5.28 (1 H, t, J 6.2), 6.86 (2 H, d, J 8.0),
6.93 (1 H, t, J 7.3), 7.19–7.27 (3 H, m), 7.39 (1 H, s), 7.47
(1 H, d, J 8.4); δC(75 MHz; CDCl3) 13.7, 22.3, 27.5, 31.8, 82.3,
115.4, 121.6, 126.9, 129.5, 130.2, 130.3, 132.3, 137.4, 157.8 and
200.5.
1-Phenyl-2-(2-ethylphenoxy)pentan-1-one 6e. Purified by col-
umn chromatography (hexane–EtOAc = 40:1) to give white
crystals (0.95 g, 72%), mp 56–57 ЊC (Found: C, 80.58; H, 8.02.
Calc. for C19H22O2: C, 80.82; H, 7.85%); δH(300 MHz; CDCl3)
1062
J. Chem. Soc., Perkin Trans. 1, 1998

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0.99 (3 H, t, J 7.4), 1.25 (3 H, t, J 7.5), 1.57–1.67 (2 H, m), 1.98–
2.12 (2 H, m), 2.75 (2 H, q, J 7.1), 5.30 (1 H, dd, J 4.7, 8.3), 6.60
(1 H, d, J 8.0), 6.84 (1 H, t, J 7.3), 7.00 (1 H, t, J 7.3), 7.13 (1 H,
d, J 7.2), 7.43 (2 H, t, J 7.6), 7.54 (1 H, t, J 7.4), 8.09 (2 H, d, J
7.2); δC(75 MHz; CDCl3) 13.8, 14.2, 19.1, 23.3, 35.4, 80.8,
111.4, 121.0, 126.6, 128.6, 128.7, 129.2, 132.8, 133.4, 134.5,
155.4 and 199.3.
1-(4-Methylphenyl)-2-(4-methylphenylthio)propan-1-one 6h.
Purified by column chromatography (hexane–EtOAc = 20:1) to
give a colourless oil (1.09 g, 81%) (Found: C, 75.32; H, 6.90.
Calc. for C17H18OS: C, 75.52; H, 6.71%); δH(300 MHz; CDCl3)
1.51 (3 H, d, J 6.9), 2.35 (3 H, s), 2.44 (3 H, s), 4.56 (1 H, q, J
6.8), 7.10 (2 H, d, J 8.0), 7.24–7.29 (4 H, m), 7.89 (2 H, d, J 8.2);
δC(75 MHz; CDCl3) 16.9, 21.2, 21.6, 46.2, 128.1, 128.8, 129.3,
129.7, 133.2, 135.1, 138.9, 143.8 and 195.9.
1-(4-Chlorophenyl)-2-(1-naphthyloxy)-5-phenylpentan-1-one
15a. Purified by column chromatography (hexane–EtOAc =
20:1) to give a colourless oil (1.53 g, 74%) (Found: C, 78.18; H,
5.94. Calc. for C27H23O2Cl: C, 78.23; H, 5.60%); δH(300 MHz;
CDCl3) 1.90–2.35 (4 H, m), 2.73 (2 H, t, J 7.4), 5.33 (1 H, dd, J
4.1, 8.2), 6.57 (1 H, d, J 7.8), 7.16–7.51 (11 H, m), 7.75–7.78 (1
H, m), 8.03 (2 H, d, J 8.7), 8.35–8.38 (1 H, m); δC(75 MHz;
CDCl3) 27.2, 32.7, 35.3, 82.0, 105.6, 121.2, 121.9, 125.5, 125.6,
125.7, 126.0, 126.6, 127.6, 128.4, 129.0, 130.2, 132.5, 134.7,
140.1, 141.4, 153.3 and 198.1.
1-Phenyl-4-(1-naphthyloxy)octan-3-one 15b. Purified by col-
umn chromatography (hexane–EtOAc = 20:1) to give a colour-
less oil (1.39 g, 80%) (Found: C, 83.22; H, 7.76. Calc. for
C24H26O2: C, 83.20; H, 7.56%); δH(300 MHz; CDCl3) 0.89 (3 H,
t, J 7.1), 1.28–1.56 (4 H, m), 1.75–1.87 (1 H, m), 1.89–2.02 (1 H,
m), 2.67–3.05 (4 H, m), 4.66 (1 H, dd, J 4.9, 8.2), 6.52 (1 H, d, J
7.5), 7.05 (2 H, d, J 6.6), 7.10–7.29 (5 H, m), 7.43 (1 H, d, J 8.1),
7.48–7.52 (2 H, m), 7.79–7.82 (1 H, m), 8.32–8.35 (1 H, m);
δC(75 MHz; CDCl3) 13.8, 22.4, 27.5, 29.0, 32.0, 38.5, 83.4,
105.2, 121.1, 122.0, 125.5, 125.6, 125.7, 126.0, 126.6, 127.6,
128.4, 134.7, 140.8, 153.5 and 211.5.
colourless oil (1.26 g, 79%) (Found: C, 86.34; H, 8.76. Calc.
for C23H28O: C, 86.20; H, 8.81%); δH(300 MHz; CDCl3) 0.87
(3 H, t, J 6.7), 1.18–1.40 (10 H, m), 1.72–1.81 (2 H, m), 2.43
(3 H, s), 2.84 (2 H, t, J 7.7), 7.18–7.30 (4 H, m), 7.38 (2 H, d,
J 8.0), 7.45 (1 H, d, J 7.4), 7.54 (1 H, d, J 8.2); δC(75 MHz;
CDCl3) 14.1, 21.3, 22.7, 26.8, 28.4, 29.2, 29.3, 29.4, 31.9, 110.8,
116.6, 119.5, 122.5, 123.4, 129.0, 129.1, 129.4, 129.9, 136.7,
154.0 and 155.2.
2-Methyl-3-(4-methylphenyl)benzo[b]furan 7c. Purified by
column chromatography (hexane–EtOAc = 20:1) to give a col-
ourless oil (0.88 g, 80%); m/z (EI) 222.1055 (Mϩ). C16H14O
requires 222.1045; δH(300 MHz; CDCl3) 2.45 (3 H, s), 2.55 (3 H,
s), 7.20–7.33 (4 H, m), 7.41–7.48 (3 H, m), 7.59 (1 H, d, J 7.1);
δC(75 MHz; CDCl3) 12.8, 21.2, 110.7, 116.8, 119.4, 122.5,
123.4, 128.8, 129.4, 129.8, 130.0, 136.6, 151.0 and 154.1.
2-Butyl-3-(2,4-dichlorophenyl)benzo[b]furan 7d. Purified by
column chromatography (hexane–EtOAc = 40:1) to give a col-
ourless oil (0.94 g, 59%) (Found: C, 68.28; H, 5.54. Calc. for
C18H16Cl2O: C, 67.91; H, 5.07%); δH(300 MHz; CDCl3) 0.88 (3
H, t, J 7.3), 1.28–1.40 (2 H, m), 1.64–1.82 (2 H, m), 2.58–2.80 (2
H, m), 7.18–7.37 (5 H, m), 7.49 (1 H, d, J 8.0), 7.58 (1 H, s);
δC(75 MHz; CDCl3) 13.7, 22.3, 26.8, 29.9, 110.9, 113.8, 119.7,
122.6, 123.6, 127.2, 128.8, 129.8, 130.4, 133.0, 134.3, 135.4,
153.9 and 156.4.
2-(3-Phenylpropyl)-3-(4-chlorophenyl)naphtho[1,2-b]furan
16a. Purified by column chromatography (hexane–EtOAc =
40:1) to give a colourless oil (1.41 g, 71%); m/z (EI) 396.1298
(Mϩ). C27H21ClO requires 396.1281; δH(300 MHz; CDCl3) 2.13–
2.23 (2 H, m), 2.71 (2 H, t, J 7.4), 2.96 (2 H, t, J 7.4), 7.14–7.29 (6
H, m), 7.38–7.50 (4 H, m), 7.57–7.68 (3 H, m), 7.93 (1 H, d, J 8.2),
8.32 (1 H, d, J 8.2); δC(75 MHz; CDCl3) 26.3, 30.1, 35.3, 117.4,
118.1, 119.9, 121.2, 123.4, 123.7, 124.9, 125.9, 126.3, 128.4,
128.5, 129.0, 130.4, 131.3, 131.4, 133.0, 141.5, 149.4 and 154.2.
Preparation of 2-methyl-3-(4-methylphenyl)-5-methylbenzo[b]-
thiophene 7h and 2-propyl-3-(2-phenylethyl)naphtho[1,2-b]-
thiophene 16d
1-Phenyl-4-(1-naphthylthio)heptan-3-one 15d. Purified by
column chromatography (hexane–EtOAc = 8:1) to give a semi
crystalline solid (1.62 g, 93%) (Found: C, 79.04; H, 7.00. Calc.
for C23H24OS: C, 79.27; H, 6.94%); δH(300 MHz; CDCl3) 0.90
(3 H, t, J 7.3), 1.30–1.56 (2 H, m), 1.64–1.87 (2 H, m), 2.83–2.95
(4 H, m), 3.71 (1 H, t, J 7.5), 7.11–7.25 (6 H, m), 7.33 (1 H, d, J
8.5), 7.42–7.49 (2 H, m), 7.70–7.77 (4 H, m); δC(75 MHz;
CDCl3) 13.7, 20.5, 30.0, 32.4, 40.9, 56.9, 126.0, 126.2, 126.4,
126.6, 127.5, 127.7, 128.4, 128.6, 129.3, 131.2, 132.5, 133.6,
140.9 and 206.4.
To the corresponding 1-(4-methylphenyl)-2-(4-methylphenyl-
thio)propan-1-one 6h (5 mmol, 1.28 g) or 1-phenyl-4-(1-
naphthylthio)heptan-3-one 15d (5 mmol, 1.74 g) polyphos-
phoric acid (10 g) was added at room temperature and the reac-
tion mixture was heated at 120–125 ЊC for 20 h. Upon cooling,
the oily residue was dissolved in Et2O, poured into ice–water
(100 cm3) and extracted with Et2O (3 × 50 cm3). The combined
organic layer was dried (Na2SO4) and the solvent was evapor-
ated in vacuo. The residue was purified by column chroma-
tography to give the corresponding product 7h or 16d.
General procedure for the preparation of polysubstituted
benzo[b]furans 7a–d and 2-(3-phenylpropyl)-3-(4-chlorophenyl)-
naphtho[1,2-b]furan 16a. A mixture of the corresponding α-
aryloxy ketone 6 or 1-(4-chlorophenyl)-2-(1-naphthyloxy)-5-
phenylpentan-1-one 15a (5 mmol) and ZnBr2 (10 mmol, 2.3 g)
was heated at 175–180 ЊC for 10–24 h. On cooling, the oily
residue was dissolved in Et2O, filtered, quenched with water
(50 cm3) and extracted with Et2O (3 × 50 cm3). The combined
organic layers were dried (Na2SO4), and the solvent was
evaporated in vacuo. The crude product was purified by column
chromatography to give the corresponding products 7 or 16a.
2-Benzyl-3-(2-phenylethyl)benzo[b]furan 7a. Purified by col-
umn chromatography (hexane–EtOAc = 40:1) to give a colour-
less oil (1.25 g, 80%) (Found: C, 88.93; H, 6.72. Calc. for
C23H20O: C, 88.43; H, 6.45%); δH(300 MHz; CDCl3) {data
in square brackets are given for the regioisomer, 2-(2-
phenylethyl)-3-benzylbenzo[b]furan; the ratio of the products,
according to the GC–MS data, was 13:1} 2.90–3.06 (4 H, m),
[3.84 (2 H, s)], 3.88 (2 H, s), 7.07–7.30 (14 H, m), [7.37–7.53
(14 H, m)]; δC(75 MHz; CDCl3) 26.1, 32.5, 36.0, 111.0, 114.6,
119.0, 122.1, 123.4, 126.1, 126.5, 128.3, 128.4, 128.5, 137.8,
141.6, 152.7 and 154.3.
2-Methyl-3-(4-methylphenyl)-5-methylbenzo[b]thiophene 7h.
Purified by column chromatography (hexane–EtOAc = 40:1) to
give a colourless oil (1.02 g, 81%) (Found: C, 80.98; H, 6.48.
Calc. for C17H16S: C, 80.91; H, 6.39%); δH(300 MHz; CDCl3)
2.36 (3 H, s), 2.42 (3 H, s), 2.45 (3 H, s), 7.06–7.10 (2 H, m),
7.24–7.30 (4 H, m), 7.63 (1 H, d, J 8.2); δC(75 MHz; CDCl3)
14.5, 21.3, 21.4, 121.6, 122.5, 125.4, 129.2, 129.9, 132.5, 133.5,
133.8, 135.3, 136.0 and 136.8.
2-Propyl-3-(2-phenylethyl)naphtho[1,2-b]thiophene 16d. Puri-
fied by column chromatography (hexane–EtOAc = 40:1) to give
white crystals (2.74 g, 83%), mp 78–79 ЊC (Found: C, 83.36; H,
6.53.Calc.forC23H22S:C,83.60;H,6.72%);δH(300MHz;CDCl3)
1.03 (3 H, t, J 7.3), 1.67–1.79 (2 H, m), 2.78 (2 H, t, J 7.7), 3.09 (2
H, t, J 8.1), 3.55 (2 H, t, J 8.1), 7.27–7.39 (5 H, m), 7.55 (1 H, t,
J 7.2), 7.65 (1 H, t, J 8.3), 7.71 (1 H, d, J 8.7), 7.84 (1 H, d, J 8.7),
7.99 (1 H, d, J 8.2), 8.72 (1 H, d, J 8.3); δC(75 MHz; CDCl3)
14.0, 24.9, 30.6, 31.1, 35.8, 120.9, 123.2, 124.5, 126.0, 126.2,
128.5, 129.3, 129.9, 132.2, 133.2, 133.8, 136.7, 141.0 and 141.6.
One-pot procedure for the preparation of polysubstituted
benzo[b]furans 7a–f, benzo[b]thiophenes 7g, 7h, naphtho[1,2-b]-
furans 16a, 16b, and naphtho[1,2-b]thiophenes 16c, 16d
To a stirred solution of the corresponding 1-[aryloxy(thio)-
2-Octyl-3-(4-methylphenyl)benzo[b]furan 7b. Purified by
column chromatography (hexane–EtOAc = 40:1) to give a
J. Chem. Soc., Perkin Trans. 1, 1998
1063

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methyl]benzotriazoles 3a–3e or 1-[naphthyloxy(thio)methyl]-
benzotriazoles 12a,b (5 mmol) in dry THF (50 cm3) at Ϫ78 ЊC
under argon, BunLi (1.6 , 3.8 cm3, 5.5 mmol) was added.
After 1 h, the appropriate electrophile (5.5 mmol) [benzyl brom-
ide (0.94 g) for 7a,g and 16c, n-octyl iodide (1.32 g) for 7b,
methyl iodide (0.78 g) for 7c,h, n-butyl bromide (0.75 g) for 7d
and 16b, n-propyl iodide (0.93 g) for 7e and 16d, n-hexyl brom-
ide (0.91 g) for 7f, and 1-bromo-3-phenylpropane (1.10 g) for
16a] in THF (5 cm3) was added. The mixture was stirred at
Ϫ78 ЊC for an additional 3 h and then at room temperature
overnight. The reaction solution was cooled down to Ϫ78 ЊC
and a second equivalent of BunLi (1.6 , 3.8 cm3, 5.5 mmol)
was added. After 2 min, the appropriate aldehyde (5.5 mmol)
[hydrocinnamaldehyde (0.74 g) for 7a,g and 16b,d, 4-methyl-
benzaldehyde (0.66 g) for 7b,c,h, 2,4-dichlorobenzaldehyde
(0.96 g) for 7d, benzaldehyde (0.58 g) for 7e, and 4-
chlorobenzaldehyde (0.77 g) for 7f and 16a,c] in THF (5 cm3)
was added. The mixture was stirred at Ϫ78 ЊC for an additional
3 h and then at room temperature overnight. A solution of
ZnBr2 (12 mmol, 2.7 g) in THF (10 cm3) was added, and the oily
residue was heated at 140 ЊC for 10 h.
2-Butyl-3-(2-phenylethyl)naphtho[1,2-b]furan 16b. Purified by
column chromatography (hexane–EtOAc = 40:1) to give a
colourless oil (1.20 g, 73%) (Found: C, 87.65; H, 7.74. Calc. for
C24H24O: C, 87.76; H, 7.36%); δH(300 MHz; CDCl3) 0.92 (3 H,
t, J 7.3), 1.28–1.40 (2 H, m), 1.58 (2 H, quintet, J 7.4), 2.61 (2 H,
t, J 7.4), 2.94–2.98 (4 H, m), 7.13–7.28 (5 H, m), 7.43 (1 H, t, J
7.0), 7.52–7.63 (3 H, m), 7.91 (1 H, d, J 8.2), 8.26 (1 H, d, J 8.2);
δC(75 MHz; CDCl3) 13.8, 22.4, 26.1, 30.7, 36.5, 114.4, 118.1,
119.8, 121.3, 122.5, 124.4, 124.8, 125.96, 126.0, 128.3, 128.4,
128.6, 130.9, 141.7, 149.1 and 154.5.
2-Benzyl-3-(4-chlorophenyl)naphtho[1,2-b]thiophene
16c.
Purified by column chromatography (hexane–EtOAc = 40:1) to
give white crystals (1.49 g, 78%), mp 123–124 ЊC (Found: C,
78.21; H, 4.50. Calc. for C25H17ClS: C, 78.11; H, 4.46%); δH(300
MHz; CDCl3) 4.03 (2 H, s), 7.14 (2 H, d, J 6.9), 7.20–7.35 (6 H,
m), 7.40 (1 H, t, J 7.4), 7.48–7.53 (3 H, m), 7.69 (1 H, d, J 8.8),
7.79 (1 H, d, J 8.8), 7.88 (1 H, d, J 8.0); δC(75 MHz; CDCl3)
34.8, 120.5, 123.4, 124.8, 125.2, 125.7, 126.5, 128.5, 128.6,
129.3, 129.6, 131.7, 132.0, 133.7, 133.9, 135.1, 136.7, 136.8,
140.0 and 141.2.
References
Method A: preparation of benzo[b]furans 7a–f and naphtho-
[1,2-b]furan 16a
1 P. Cagniant and D. Cagniant, in Advances in Heterocyclic Chemistry,
eds. A. R. Katritzky and A. J. Boulton, Academic Press, New York,
1975, vol. 18, p. 338.
2 E. Campaigne, in Comprehensive Heterocyclic Chemistry, eds. C. W.
Bird and G. W. H. Cheeseman, Pergamon, Oxford, 1984, vol. 4,
p. 910.
3 B. A. Keay and P. W. Dibble, in Comprehensive Heterocyclic
Chemistry II, eds. A. R. Katritzky, C. W. Rees and E. F. V. Scriven,
Pergamon, Oxford, 1996, vol. 2, p. 395.
4 R. K. Russel, in Comprehensive Heterocyclic Chemistry II, eds. A. R.
Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon, Oxford, 1996,
vol. 2, p. 679.
The reaction mixture was heated at 175–180 ЊC for 10–24 h.
Upon cooling, the oily residue was dissolved in Et2O, filtered,
quenched with water (50 cm3), and extracted with Et2O (3 × 50
cm3). The combined organic layers were dried (Na2SO4), and
solvent was evaporated in vacuo. The residue was purified by
column chromatography to give the corresponding compounds
7a–f or 16a.
Method B: preparation of benzo[b]thiophenes 7g, 7h, naphtho-
[1,2-b]furan 16b and naphtho[1,2-b]thiophenes 16c,d
5 R. P. Haugland, in Handbook of Fluorescent Probes and Research
Chemicals, ed. M. T. Z. Spence, Molecular Probes, Inc., Eugene,
OR, 1996.
To the crude oily residue polyphosphoric acid (10 g) was added
at room temperature, and the reaction mixture was heated at
120–125 ЊC for 20 h. Upon cooling, the oily residue was dis-
solved in Et2O, poured into ice–water (100 cm3) and extracted
with Et2O (3 × 50 cm3). The combined organic layer was dried
(Na2SO4) and the solvent was evaporated in vacuo. The crude
product was purified by column chromatography to give the
corresponding products 7g, 7h or 16b–d. The appearance and
NMR spectral data for compounds 7a–d, 7h and 16a, 16d were
identical to those described above (cyclization of 6 into 7 and
15 into 16).
2-Propyl-3-phenyl-7-ethylbenzo[b]furan 7e. Purified by col-
umn chromatography (hexane–EtOAc = 40:1) to give a colour-
less oil (0.95 g, 72%); m/z (EI) 264.1511 (Mϩ). C19H20O requires
264.1514; δH(300 MHz; CDCl3) 0.99 (3 H, t, J 7.3), 1.38 (3 H, t,
J 7.6), 1.75–1.87 (2 H, m), 2.84 (2 H, t, J 7.4), 2.96 (2 H, q, J
7.6), 7.07–7.17 (2 H, m), 7.33–7.39 (2 H, m), 7.44–7.48 (4 H, m);
δC(75 MHz; CDCl3) 13.9, 14.2, 21.9, 23.0, 28.8, 117.0, 122.7,
122.8, 126.9, 127.4, 128.5, 128.7, 129.2, 133.2, 152.5 and 154.7.
2-Hexyl-3-(4-chlorophenyl)-4,5,6-trimethylbenzo[b]furan 7f.
Purified by column chromatography (hexane–EtOAc = 40:1) to
give a colourless oil (1.12 g, 64%) (Found: C, 78.19; H, 8.08.
Calc. for C23H27ClO: C, 77.93; H, 7.68%); δH(300 MHz; CDCl3)
0.87 (3 H, t, J 6.0), 1.19–1.36 (6 H, m), 1.61–1.70 (2 H, m), 2.04
(3 H, s), 2.21 (3 H, s), 2.41 (3 H, s), 2.57 (2 H, t, J 4.9), 7.17 (1 H,
s), 7.28 (2 H, d, J 8.5), 7.41 (2 H, d, J 7.8); δC(75 MHz; CDCl3)
14.0, 15.0, 16.1, 22.5, 26.3, 28.3, 28.8, 31.5, 109.4, 116.3, 125.6,
128.3, 128.5, 129.4, 132.1, 132.6, 133.2, 133.5, 152.2 and 154.9.
6 (a) M. Iwasaki, J. Li, Y. Kobayashi, H. Matsuzaka, Y. Ishii and
M. Hidai, Tetrahedron Lett., 1989, 30, 95; (b) J. W. Terpstra and
A. M. van Leusen, J. Org. Chem., 1986, 51, 230; (c) A. M. van
Leusen and J. W. Terpstra, Tetrahedron Lett., 1981, 22, 5097; (d)
A. R. Katritzky, L. Serdyuk, L. Xie and I. Ghiviriga, J. Org. Chem.,
1997, 62, 6215; (e) W. T. Brady, Y. F. Giang, A. P. Marchand and
A. Wu, J. Org. Chem., 1987, 52, 3457; ( f ) A. Hercouet and M. Le
Corre, Tetrahedron, 1981, 37, 2867; (g) G. Pandey, A. Krishna and
U. T. Bhalerao, Tetrahedron Lett., 1989, 30, 1867; (h) T. J. Barton
and B. L. Groh, J. Org. Chem., 1985, 50, 158; (i) R. E.
Koenigkramer and H. Zimmer, J. Org. Chem., 1980, 45, 3994; (j)
P. D. Seemuth and H. Zimmer, J. Org. Chem., 1978, 43, 3063; (k)
A. R. Katritzky, X. Lan and Z. Zhang, J. Heterocycl. Chem., 1993,
30, 381; (l) F. Johnson and R. Subramanian, J. Org. Chem., 1986,
51, 5040; (m) R. Leardini, G. F. Pedulli, A. Tundo and G. Zanardi,
J. Chem. Soc., Chem. Commun., 1985, 1390; (n) R. D. Stephens and
C. E. Castro, J. Org. Chem., 1963, 28, 3313.
7 W. Fridrichsen, in Comprehensive Heterocyclic Chemistry II, eds.
A. R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon, Oxford,
1996, vol. 2, p. 351.
8 J. Nakayama, in Comprehensive Heterocyclic Chemistry II, eds. A. R.
Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon, Oxford, 1996,
vol. 2, p. 607.
9 B. Iddon and R. M. Scrowston, in Advances in Heterocyclic
Chemistry, eds. A. R. Katritzky and A. J. Boulton, Academic Press,
New York, 1970, vol. 11, p. 178.
10 W. R. Boehme, in Org. Synth., 1963, 4, 590.
11 P. Barker, P. Finke and K. Thompson, Synth. Commun., 1989, 19,
257.
12 N. B. Chapman, K. Clarke and S. N. Sawhney, J. Chem. Soc. (C),
1968, 518.
13 R. Royer and L. Rene, Bull. Soc. Chim. Fr., 1970, 1037.
14 A. R. Katritzky, L. Xie and L. Serdyuk, J. Org. Chem., 1996, 61, 7564.
15 R. P. Dickinson and B. Iddon, J. Chem. Soc. (C), 1968, 2733.
16 A. R. Katritzky, S. Rachwal and B. Rachwal, J. Org. Chem., 1989,
54, 6022.
2-Benzyl-3-(2-phenylethyl)-5-chlorobenzo[b]thiophene
7g.
Purified by column chromatography (hexane–EtOAc = 40:1) to
give a colourless oil (1.41 g, 78%) (Found: C, 76.50; H, 5.56.
Calc. for C23H19ClS: C, 76.12; H, 5.28%); δH(300 MHz; CDCl3)
2.85 (2 H, t, J 7.7), 3.09 (2 H, t, J 7.7), 3.90 (2 H, s), 7.09–7.16
(4 H, m), 7.21–7.32 (7 H, m), 7.63–7.66 (2 H m); δC(75
MHz; CDCl3) 28.9, 34.3, 35.8, 121.1, 123.3, 124.0, 126.2, 126.7,
128.5, 128.6, 130.3, 130.7, 137.0, 139.4, 141.2, 141.3 and 141.5.
Paper 7/08809D
Received 8th December 1997
Accepted 19th December 1997
1064
J. Chem. Soc., Perkin Trans. 1, 1998