Synthesis of 2,3-Bis(arylamino)benzofurans and 2,3-Bis(arylimino)-2,3- dihydrobenzofurans by a Lewis Acid Catalyzed Reaction of 2-Aryliminophenols with Aryl Isocyanides

Article abstract of DOI:10.1055/s-0029-1218609

An efficient method for the preparation of 2,3-bis(arylamino)benzofurans and 2,3-bis(arylimino)-2,3-dihydrobenzofurans is described that is based on the reaction of 2-aryliminophenols with aryl isocyanides in the presence of a catalytic amount of boron trifluoride diethyl etherate. The reaction gives 2,3-bis(arylamino)benzofurans, some of which are transformed into 2,3-bis(arylimino)-2,3-dihydrobenzofurans by air oxidation, mostly during workup. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0029-1218609

666
PAPER
Synthesis of 2,3-Bis(arylamino)benzofurans and 2,3-Bis(arylimino)-2,3-dihy-
drobenzofurans by a Lewis Acid Catalyzed Reaction of 2-Aryliminophenols
with Aryl Isocyanides
2
, 3-Bis(arylamino)
a
benzofuran
z
s
a
nd 2,3-B
u
is(arylimino
h
)-2,3-dihydr
i
obenzo
r
furans o Kobayashi,* Yuu Shirai, Shuhei Fukamachi, Hisatoshi Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University,
4-101 Koyama-minami, Tottori 680-8552, Japan
Fax +81(857)315263; E-mail: kkoba@chem.tottori-u.ac.jp
Received 6 October 2009; revised 6 November 2009
obtained in moderate yields; the moderate yields were
Abstract: An efficient method for the preparation of 2,3-bis(aryl-
probably caused by oxidation of the initially formed 2,3-
bis(arylamino)benzofurans 2 during workup, as illustrat-
ed in Scheme 1. Although the stereochemistries of the 2-
amino)benzofurans and 2,3-bis(arylimino)-2,3-dihydrobenzofurans
is described that is based on the reaction of 2-aryliminophenols with
aryl isocyanides in the presence of a catalytic amount of boron tri-
fluoride diethyl etherate. The reaction gives 2,3-bis(arylamino)ben- and 3-imino moieties of the products 3 could not be con-
zofurans, some of which are transformed into 2,3-bis(arylimino)-
firmed spectroscopically, we tentatively assigned them as
2,3-dihydrobenzofurans by air oxidation, mostly during workup.
2-(Z) and 3-(Z) because these conformations give the least
Key words: benzofurans, o-hydroxybenzylideneamines, isocya-
nides, boron trifluoride, imidoyl cations
sterically crowded structures. We were unable to prepare
the corresponding 2,3-diimino-2,3-dihydrobrnzofuran de-
rivative using tert-butyl isocyanide in place of aryl isocy-
anides; in this case, progress of the reaction was extremely
Because some molecules containing a benzofuran moiety sluggish and the starting material 1a was recovered almost
are known to display a variety of biological activities,1 the quantitatively after overnight reaction at room tempera-
development of new, efficient methods for the synthesis ture. One of the reasons for this may be ascribed to the
of benzofurans continues to be of interest.2 In this paper steric bulk of this isocyanide.
we report a facile preparation of 2,3-diaminobenzofuran
derivatives, 2,3-bis(arylimino)-2,3-dihydrobenzofurans
NHPh
cat. BF3
•OEt2
and 2,3-bis(arylamino)benzofurans, by a Lewis acid cata-
lyzed reaction of readily available 2-aryliminophenols
with aryl isocyanides. There have been only a few reports
on the synthesis of these types of benzofuran derivatives.3
A synthesis of 2,3-bis(arylimino)-2,3-dihydrophenan-
thro[9,10-b]furans has been achieved by successive treat-
ment of RCOC(=N2)COR (RR=2,2¢-biphenylene) with
Ph3P=NAr1 and Ar2NC.3a 2-Alkyl(or phenyl)amino-3-(2-
hydroxybenzylideneamino)benzofurans have been pre-
pared in lower yields under the conditions of the Ugi four-
component (isocyanides, ammonium formate and two
equivalents of 2-hydroxybenzaldehydes) condensation.3b
Ph
CH2Cl2, 0 °C
N
+
NHAr
ArNC
O
OH
1a
2
Ph
N
N
workup, [O]
O
Ar
3a Ar = o-Tol 58%
3b Ar = 2,5-Xylyl 49%
3c Ar = 4-Cl-2-MeC6H3 47%
3d Ar = 5-Cl-2-MeC6H3 48%
3e Ar = 4-MeO-2-MeC6H3 52%
Scheme 1 Preparation of 2,3-diimino-2,3-dihydrobenzofurans
2-(Phenylimino)phenol (1a), which is available from 2-
hydroxybenzaldehyde and aniline, was chosen as the first
substrate and allowed to react with several aromatic iso-
cyanides in dichloromethane at 0 °C in the presence of a
catalytic amount of a Lewis acid. We chose boron trifluo-
ride diethyl etherate as a Lewis acid because we have pre-
viously had much success in heterocycle syntheses using
this Lewis acid in catalyzed reactions utilizing isocya-
nides.4 As expected, the reactions proceeded smoothly
and cleanly. After usual workup followed by purification
of the crude products by column chromatography on silica
gel, 2,3-bis(arylimino)-2,3-dihydrobenzofurans 3 were
Next, 2-[4-chlorophenylimino]phenol (1b), which is
available by condensation of 2-hydroxybenzaldehyde
with 4-chlorobenzeneamine, was treated with 1-isocyano-
4-methoxy-2-methylbenzene according to the procedure
described above. The reaction gave a mixture of the cor-
responding 2,3-diaminobenzofuran derivative 2f and 2,3-
diimino-2,3-dihydrobenzofuran derivative 3f, as judged
by 1H NMR of the crude material after workup. Standing
a solution of this mixture in hexane–diethyl ether (1:1) in
air overnight at room temperature effected the oxidation
of 2f to 3f, and enabled the isolation of 3f in pure form
(53%) by simply collecting the precipitate that appeared
in the solution (Scheme 2).
SYNTHESIS 2010, No. 4, pp 0666–0670
x
x
.
x
x
.2
0
1
0
Advanced online publication: 16.12.2009
DOI: 10.1055/s-0029-1218609; Art ID: F19709SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
2,3-Bis(arylamino)benzofurans and 2,3-Bis(arylimino)-2,3-dihydrobenzofurans
667
Cl
R1
Ph
N
1b or
+
OMe
N
R2
Cl
OH
CN
+
1c
OH
CN
R4
1b
HN
cat. BF3•OEt2, CH2Cl2, 0 °C
NH
Cl
NH
R1
R3
O
NH
O
R2
2g R1 = Me, R2 = R3 = H, R4 = Cl 72%
2h R1 = Me, R2 = R4 = H, R3 = Cl 60%
2i R1 = H, R2 = R3 = Cl, R4 = H 74%
2j R1 = Me, R2 = R3 = Cl, R4 = H 69%
2f
OMe
1) cat. BF3•OEt2, CH2Cl2, 0 °C
+
2) workup
N
Cl
Scheme 3 preparation of 2,3-diaminobenzofurans
N
phenol 1, which is activated by boron trifluoride, to gen-
erate an imidoyl cation intermediate 4. This cation center
is trapped through intramolecular attack of the hydroxy
oxygen to give an oxonium ion intermediate 5. Deproto-
nation and removal of boron trifluoride gives 3-arylami-
no-2-arylimino-2,3-dihydrobenzofuran 6, which then
tautomerizes to 2. The results described above imply that:
(1) the oxidation of 2 to 3 is inhibited by substitution of a
chloro group on the benzene rings of 2-(arylimino)phe-
nols 1; (2) the substitution of a methoxy group on the 4-
position of isocyanides facilitates the oxidation.
O
3f
OMe
air
3f 53%
Scheme 2 Formation of a 2,3-diamino-2,3-dihydrobenzofuran
A similar Lewis acid catalyzed reaction of 1b with 1-iso-
cyano-2-methylbenzene followed by workup and purifi-
cation by column chromatography on silica gel, however,
provided the corresponding 2,3-diaminobenzofuran de-
rivative 2g, in a fair yield; this compound was found to be
considerably more stable toward oxidation. Subsequently,
the reaction of 5-chloro-2-phenyliminophenol (1c), which
is accessible by condensation of 4-chloro-2-hydroxyben-
zaldehyde with aniline, with aryl isocyanides, proved to
give similar results. Thus, treatment of 1c with aryl isocy-
anides in a manner similar to that described above gave
the corresponding 2,3-bis(arylamino)benzofurans 2h–j,
as outlined in Scheme 3. Yields for the preparation of
these products, which are also summarized in Scheme 3,
are generally fair-to-good.
Ar1
N
Ar2NC
+
R
OH
1
F3B
F3B
NAr1
OH
NAr1
OH
NAr2
NAr2
BF3•OEt2
R
R
4
4'
F3B
NAr1
NHAr1
NAr2
2
NAr2
O
O
R
R
It should be noted that the attempted reactions of 2-(tert-
H
butylimino)phenol,
2-(4-methoxyphenylimno)phenol,
6
5
and 5-methoxy-2-phenyliminophenol with 1-isocyano-2-
methylbenzene under conditions similar to those men-
tioned above, only resulted in almost quantitative recov-
ery of the starting material in each case, i.e. no reactions
occurred. Elevating the reaction temperature to reflux re-
sulted in the formation of intractable mixtures of products.
The methoxy substituent is thought to decrease the reac-
tivity of these substrates in the present Lewis acid reaction
due to its electron-donating property.
Scheme 4 A probalble pathway to the products
In summary, the synthesis of 2,3-bis(arylimino)-2,3-dihy-
drobenzofurans and 2,3-bis(arylamino)benzofurans,
based on the reaction of 2-aryliminophenols with aryl iso-
cyanides catalyzed by a Lewis acid, has been achieved.
The present procedure can serve as the first practical
method for the synthesis of 2,3-diaminobenzofuran deriv-
atives. The ready availability of the starting materials and
the simplicity of the operations make the present method
attractive.
A probable pathway to 2,3-diaminobenzofurans 2 is de-
picted in Scheme 4. Thus, the isocyano-carbon of an aryl
isocyanide attacks the imino-carbon of the 2-arylimino-
Synthesis 2010, No. 4, 666–670 © Thieme Stuttgart · New York

668
K. Kobayashi et al.
PAPER
1H NMR: d = 2.33 (s, 3 H), 6.74 (d, J = 7.3 Hz, 1 H), 6.88 (dd,
J = 7.8, 7.3 Hz, 1 H), 7.07–7.11 (m, 3 H), 7.15 (d, J = 8.2 Hz, 1 H),
7.21 (dd, J = 8.2, 1.8 Hz, 1 H), 7.26 (t, J = 7.3 Hz, 1 H), 7.42–7.47
(m, 4 H).
13C NMR: d = 18.19, 112.31, 118.01, 118.20, 122.68, 123.64,
125.21, 126.08, 126.11, 128.74, 129.47, 130.24, 132.72, 134.92,
142.55, 150.23, 150.49, 153.44, 160.5.
All melting points were obtained on a Laboratory Devices MEL-
TEMP II melting point apparatus and are uncorrected. IR spectra
were determined with a Shimadzu FTIR-8300 spectrophotometer.
The 1H NMR spectra were determined in CDCl3 using TMS as an
internal reference with a JEOL ECP500 FT NMR spectrometer op-
erating at 500 MHz. The 13C NMR spectra were determined in
CDCl3 using TMS as an internal reference with a JEOL ECP500 FT
NMR spectrometer operating at 125 MHz. Low-resolution MS
spectra were measured with a JEOL JMS AX505 HA spectrometer.
TLC was carried out on Merck Kieselgel 60 PF254. Column chroma-
tography was performed using Merck Kieselgel 60 (0.063–0.200
mm). All of the organic solvents used in this study were dried over
appropriate drying agents and distilled prior to use. Isocyanides
were prepared by our previously reported procedure.5 2-Arylimi-
nophenols 1b6 and 1c7 were prepared by treating the required 2-hy-
droxybenzaldehyde with the corresponding arylamine. All other
chemicals used in this study are commercially available.
MS (EI, 70 eV): m/z (%) = 346 (30) [M]+, 331 (100).
Anal. Calcd for C21H15ClN2O: C, 72.73; H, 4.36; N, 8.08. Found: C,
72.60; H, 4.51; N, 8.01.
2-(5-Chloro-2-methylphenylimino)-3-phenylimino-2,3-dihy-
drobenzofuran (3d)
Orange viscous oil; Rf = 0.32 (THF–hexane, 1:4).
IR (neat): 1645, 1607 cm–1.
1H NMR: d = 2.30 (s, 3 H), 6.75 (d, J = 7.8 Hz, 1 H), 6.89 (t, J = 7.8
Hz, 1 H), 7.08–7.10 (m, 3 H), 7.12 (d, J = 8.2 Hz, 1 H), 7.18 (d,
J = 8.2 Hz, 1 H), 7.20 (d, J = 1.8 Hz, 1 H), 7.27 (t, J = 7.3 Hz, 1 H),
7.41–7.47 (m, 3 H).
13C NMR: d = 17.76, 112.43, 118.00, 118.20, 121.26, 123.70,
125.04, 125.26, 126.08, 129.05, 129.49, 131.25, 131.35, 134.98,
145.09, 150.45, 150.48, 153.40, 160.54.
2-(2-Methylphenylimino)-3-phenylimino-2,3-dihydrobenzofu-
ran (3a); Typical Procedure
To a stirred solution of 1a (0.20 g, 1.0 mmol) and freshly distilled
1-isocyano-2-methylbenzene (0.18 g, 1.5 mmol) in CH2Cl2 (3 mL)
at 0 °C, was added freshly distilled BF3·OEt2 (14 mg, 0.10 mmol).
After stirring for 1.5 h at the same temperature, the mixture was di-
luted with CH2Cl2 (10 mL) and sat. aq NaHCO3 (10 mL) was added.
The layers were separated and the aqueous layer was extracted with
CH2Cl2 (2 × 10 mL). The combined extracts were dried over anhy-
drous Na2SO4, concentrated and the residue was subjected to col-
umn chromatography on silica gel (Et2O–hexane, 1:9) to afford 3a.
MS (EI, 70 eV): m/z (%) = 346 (29) [M]+, 331 (100).
Anal. Calcd for C21H15ClN2O: C, 72.73; H, 4.36; N, 8.08. Found: C,
72.53; H, 4.57; N, 7.83.
2-(4-Methoxy-2-methylphenylimino)-3-phenylimino-2,3-dihy-
drobenzofuran (3e)
Orange needles; mp 153–157 °C (hexane–CH2Cl2).
Yield: 0.18 g (58%); orange solid; mp 81–83 °C (hexane–CH2Cl2).
IR (KBr): 1645, 1607 cm–1.
1H NMR: d = 2.35 (s, 3 H), 6.73 (d, J = 7.3 Hz, 1 H), 6.87 (dd,
J = 7.8, 7.3 Hz, 1 H), 7.08–7.14 (m, 4 H), 7.19–7.28 (m, 4 H), 7.41
(ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.46 (dd, J = 7.8, 7.3 Hz, 2 H).
13C NMR: d = 18.25, 112.36, 118.09, 118.23, 121.25, 123.44,
125.08, 125.14, 126.00, 126.05, 128.68, 129.43, 130.37, 134.82,
144.11, 149.80, 150.62, 153.58, 160.67.
IR (KBr): 1634, 1607 cm–1.
1H NMR: d = 2.41 (s, 3 H), 3.983 (s, 3 H), 6.69 (dd, J = 7.8, 1.4 Hz,
1 H), 6.79–6.87 (m, 3 H), 7.07 (d, J = 7.8 Hz, 2 H), 7.12 (d, J = 7.8
Hz, 1 H), 7.24 (t, J = 7.3 Hz, 1 H), 7.36 (d, J = 7.8 Hz, 1 H), 7.41
(ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.44 (dd, J = 7.8, 7.3 Hz, 2 H).
13C NMR: d = 18.76, 55.32, 111.31, 112.29, 115.65, 118.16,
118.29, 123.28, 123.48, 124.91, 126.17, 128.84, 129.42, 134.63,
136.62, 148.85, 150.89, 153.87, 157.50, 160.67.
MS (EI, 70 eV): m/z (%) = 312 (18) [M]+, 297 (100).
Anal. Calcd for C21H16N2O: C, 80.75; H, 5.16; N, 8.97. Found: C,
80.61; H, 5.28; N, 8.94.
MS (EI, 70 eV): m/z (%) = 342 (24) [M]+, 327 (100).
Anal. Calcd for C22H18N2O2: C, 77.17; H, 5.30; N, 8.18. Found: C,
77.16; H, 5.29; N, 8.00.
2-(2,5-Dimethylphenylimino)-3-phenylimino-2,3-dihydroben-
zofuran (3b)
Orange viscous oil; Rf = 0.36 (THF–pentane, 1:19).
IR (neat): 1640, 1607 cm–1.
3-(4-Chlorophenyl)imino-2-(4-methoxy-2-methylphenylimino)-
2,3-dihydrobenzofuran (3f)
1H NMR: d = 2.29 (s, 3 H), 2.36 (s, 3 H), 6.72 (d, J = 7.8 Hz, 1 H),
6.86 (dd, J = 7.8, 7.3 Hz, 1 H), 6.94 (d, J = 7.8 Hz, 1 H), 7.00 (s,
1 H), 7.08–7.11 (m, 3 H), 7.15 (d, J = 7.8 Hz, 1 H), 7.25 (t, J = 7.3
Hz, 1 H), 7.41 (ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.45 (dd, J = 7.8, 7.3
Hz, 2 H).
13C NMR: d = 17.77, 21.07, 112.40, 118.11, 118.23, 121.64,
123.39, 125.05, 125.90, 126.03, 128.64, 129.43, 130.17, 134.79,
135.58, 143.98, 149.67, 150.64, 153.58, 160.70.
A solution of 1b (0.23 g, 1.0 mmol) and freshly distilled 1-isocy-
ano-4-methoxy-2-methylbenzene (0.22 g, 1.5 mmol) in CH2Cl2 (3
mL) was treated with a catalytic amount of BF3·OEt2 in a manner
similar to that described in the typical procedure. After workup, the
residue was dissolved in Et2O–hexane (1:2, 20 mL), the solution
was allowed to stand in air overnight and the precipitated 3f was
collected.
Yield: 0.20 g (53%); orange needles; mp 204–208 °C (hexane–
CH2Cl2).
IR (KBr): 1638, 1601 cm–1.
1H NMR: d = 2.40 (s, 3 H), 3.83 (s, 3 H), 6.79–6.82 (m, 3 H), 6.91
(dd, J = 7.8, 7.3 Hz, 1 H), 7.03 (d, J = 8.7 Hz, 2 H), 7.14 (d, J = 8.2
Hz, 1 H), 7.37 (d, J = 7.8 Hz, 1 H), 7.42 (d, J = 8.7 Hz, 2 H), 7.44
(dd, J = 7.8, 7.3 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 326 (23) [M]+, 311 (100).
Anal. Calcd for C22H18N2O: C, 80.96; H, 5.56; N, 8.58. Found: C,
80.80; H, 5.61; N, 8.66.
2-(4-Chloro-2-methylphenylimino)-3-phenylimino-2,3-dihy-
drobenzofuran (3c)
13C NMR: d = 18.76, 55.33, 111.38, 112.48, 115.69, 119.72,
119.94, 123.42, 123.59, 125.97, 129.61, 130.32, 134.58, 135.01,
136.43, 148.58, 149.25, 154.33, 157.68, 160.82.
Orange needles; mp 123–127 °C (hexane–CH2Cl2).
IR (KBr): 1640, 1607 cm–1.
Synthesis 2010, No. 4, 666–670 © Thieme Stuttgart · New York

PAPER
2,3-Bis(arylamino)benzofurans and 2,3-Bis(arylimino)-2,3-dihydrobenzofurans
669
MS (EI, 70 eV): m/z (%) = 376 (25) [M]+, 361 (100).
MS (CI): m/z (%) = 383 (100) [M + 1]+.
Anal. Calcd for C22H17ClN2O2: C, 70.12; H, 4.55; N, 7.43. Found:
C, 70.07; H, 4.54; N, 7.25.
Anal. Calcd for C21H16Cl2N2O: C, 65.81; H, 4.21; N, 7.31. Found:
C, 65.78; H, 4.38; N, 7.34.
3-(4-Chlorophenyl)amino-2-(2-methylphenylamino)benzofu-
ran (2g)
Acknowledgment
Yellow viscous oil: Rf = 0.18 (CH2Cl2–hexane,1:4).
IR (neat): 3391, 1651, 1603 cm–1.
We thank Mrs. Miyuki Tanmatsu of this university for determining
mass spectra and performing combustion analyses.
1H NMR: d = 2.10 (s, 3 H), 4.80 (br s, 1 H), 5.74 (br s, 1 H), 6.60
(d, J = 7.3 Hz, 2 H), 6.73 (t, J = 7.3 Hz, 1 H), 6.84 (dd, J = 7.8, 7.3
Hz, 1 H), 7.01 (dd, J = 8.7, 2.3 Hz, 1 H), 7.04–7.14 (m, 6 H), 7.19
(d, J = 8.7 Hz, 1 H).
13C NMR: d = 17.50, 102.45, 111.74, 113.88, 116.83, 117.22,
119.19, 122.06, 122.16, 125.58, 127.06, 128.70, 129.00, 129.45,
130.74, 138.93, 145.57, 147.80, 149.57.
References
(1) For recent reports, see: (a) Young, R. J.; Borthwick, A. D.;
Brown, D.; Burns-Kurtis, C. L.; Campbell, M.; Chan, C.;
Charbaut, M.; Chung, C.; Convery, M. A.; Kelly, H. A.;
King, N. P.; Kleanthous, S.; Mason, A. M.; Pateman, A. J.;
Patikis, A. N.; Pinto, I. L.; Pollard, D. R.; Senger, S.; Shah,
G. P.; Toomey, J. R.; Watson, N. S.; Weston, H. E. Bioorg.
Med. Chem. Lett. 2008, 18, 23. (b) Ando, K.; Kawamura,
Y.; Akai, Y.; Kunitomo, J.; Yokomizo, T.; Yamashita, M.;
Ohta, S.; Ohishi, T.; Ohishi, Y. Org. Biomol. Chem. 2008, 6,
296. (c) Kirilmis, C.; Ahmedzade, M.; Servi, S.; Koca, M.;
Kizirgil, A.; Kazaz, C. Eur. J. Med. Chem. 2008, 43, 300.
(d) Rizzo, S.; Riviere, C.; Piazzi, L.; Bisi, A.; Gobbi, S.;
Bartolini, M.; Andrisano, V.; Morroni, F.; Tarozzi, A.;
Monti, J.-P.; Rampa, A. J. Med. Chem. 2008, 51, 2883.
(e) Ozturk, S. E.; Akgul, Y.; Anil, H. Bioorg. Med. Chem.
2008, 16, 4431. (f) Ettaoussi, M.; Peres, B.; Klupsch, F.;
Delagrange, P.; Boutin, J.-A.; Renard, P.; Caignard, D.-H.;
Chavatte, P.; Berthelot, P.; Lesieur, D.; Yous, S. Bioorg.
Med. Chem. 2008, 16, 4954. (g) Schultz, D. M.; Prescher, J.
A.; Kidd, S.; Marona-Lewicka, D.; Nicholas, D. E.; Monte,
A. Bioorg. Med. Chem. 2008, 16, 6242. (h) Allan, M.;
Manku, S.; Therrien, E.; Nguyen, N.; Styhler, S.; Robert,
M.-F.; Goulet, A.-C.; Petschner, A. J.; Rahil, G.; MacLeod,
A. R.; Déziel, R.; Bestrman, J. M.; Nguyen, H.; Wahhab, A.
Bioorg. Med. Chem. Lett. 2009, 19, 1218. (i) Asoh, K.;
Kochi, M.; Hyoudo, I.; Ohtsuka, T.; Masubuchi, M.;
Kawasaki, K.; Ebiike, H.; Shiratori, Y.; Fukami, T. A.;
Kondoh, O.; Tsukaguchi, T.; Ishii, N.; Aoki, Y.; Shima, N.;
Sakaitani, M. Bioorg. Med. Chem. Lett. 2009, 19, 1753.
(j) Chen, Y.; Chen, S.; Liu, X.; Cheng, H.; Ou, Y.; Cheng,
H.; Zhou, G.-C. Bioorg. Med. Chem. Lett. 2009, 19, 1851.
(k) Galal, S. A.; Abd El-All, A. S. A.; Abdallah, M. A.; El-
Diwani, H. J. Bioorg. Med. Chem. Lett. 2009, 19, 2420.
(2) For recent reports, see: (a) Gill, G. S.; Grobelny, D. W.;
Chaplin, J. H.; Flynn, B. L. J. Org. Chem. 2008, 73, 1131.
(b) Huang, X.-C.; Liu, Y.-L.; Pi, S.-F.; Wang, F.; Li, J.-H.
Org. Lett. 2008, 20, 1525. (c) Sakai, N.; Uchida, N.;
Konakahara, T. Tetrahedron Lett. 2008, 49, 3437.
MS (CI): m/z (%) = 349 (100) [M + 1]+.
Anal. Calcd for C21H17ClN2O: C, 72.31; H, 4.91; N, 8.03. Found: C,
72.26; H, 5.07; N, 8.04.
6-Chloro-2-(2-methylphenyl)amino-3-phenylaminobenzofuran
(2h)
Yellow viscous oil: Rf = 0.25 (CH2Cl2–hexane, 1:4).
IR (neat): 3391, 1651, 1603 cm–1.
1H NMR: d = 2.10 (s, 3 H), 4.80 (s, 1 H), 5.74 (s, 1 H), 6.60 (d,
J = 7.3 Hz, 2 H), 6.73 (t, J = 7.3 Hz, 1 H), 6.84 (dd, J = 7.8, 7.3 Hz,
1 H), 7.02 (dd, J = 8.7, 2.3 Hz, 1 H), 7.05 (d, J = 7.3 Hz, 1 H), 7.08–
7.14 (m, 5 H), 7.19 (d, J = 7.8 Hz, 1 H).
13C NMR: d = 17.50, 102.45, 111.74, 113.88, 116.83, 117.22,
119.19, 122.06, 122.16, 125.18, 127.06, 128.70, 129.00, 129.45,
130.74, 138.93, 145.57, 147.80, 149.57.
MS (CI): m/z (%) = 349 (100) [M + 1]+.
Anal. Calcd for C21H17ClN2O: C, 72.31; H, 4.91; N, 8.03. Found: C,
72.26; H, 5.00; N, 7.84.
6-Chloro-2-(3-chlorophenyl)amino-3-phenylaminobenzofuran
(2i)
Yellow viscous oil; Rf = 0.20 (Et2O–hexane, 1:4).
IR (neat): 3391, 1651, 1601 cm–1.
1H NMR: d = 4.91 (s, 1 H), 6.16 (s, 1 H), 6.68 (d, J = 7.8 Hz, 2 H),
6.83 (t, J = 7.3 Hz, 1 H), 6.91 (ddd, J = 7.8, 7.3, 1.8 Hz, 2 H), 7.09
(dd, J = 2.3, 1.8 Hz, 1 H), 7.13–7.21 (m, 5 H), 7.32 (d, J = 7.8 Hz,
1 H).
13C NMR: d = 102.95, 111.95, 113.86, 114.46, 116.25, 117.49,
119.40, 121.59, 122.54, 128.50, 128.89, 129.52, 130.34, 135.10,
141.89, 145.43, 147.89, 148.46.
(d) Liang, Y.; Tao, L.-M.; Zhang, Y.-H.; Li, J.-H. Synthesis
2008, 3988. (e) Eidamshaus, C.; Burch, J. D. Org. Lett.
2008, 10, 4211. (f) Lingam, V. S. P. R.; Vinodkumar, R.;
Mukkanti, K.; Thomas, A.; Gopalan, B. Tetrahedron Lett.
2008, 49, 4260. (g) Csékei, M.; Novák, Z.; Kotschy, A.
Tetrahedron 2008, 64, 8992. (h) Farrago, F. J.; Kotschy, A.
Synthesis 2009, 85. (i) Jiang, Y.; Gao, B.; Huang, W.; Liang,
Y.; Huang, G.; Ma, Y. Synth. Commun. 2009, 39, 197.
(j) Shen, Z.; Dong, V. M. Angew. Chem. Int. Ed. 2009, 48,
784. (k) Miyata, O.; Takeda, N.; Naito, T. Heterocycles
2009, 78, 843. (l) Martínez, C.; Álvarez, R.; Aurrecoechea,
J. M. Org. Lett. 2009, 11, 1083. (m) Isono, N.; Lautens, M.
Org. Lett. 2009, 11, 1329. (n) Murai, M.; Miki, K.; Ohe, K.
Chem. Commun. 2009, 3466.
MS (CI): m/z (%) = 369 (100) [M + 1]+.
Anal. Calcd for C20H14Cl2N2O: C, 65.06; H, 3.82; N, 7.59. Found:
C, 64.81; H, 3.71; N, 7.42.
6-Chloro-2-(5-chloro-2-methylphenyl)amino-3-phenylamino-
benzofuran (2j)
Beige solid; mp 124–129 °C (hexane–Et2O).
IR (KBr): 3397, 1651, 1601 cm–1.
1H NMR: d = 2.14 (s, 3 H), 4.94 (s, 1 H), 5.81 (s, 1 H), 6.70 (dd,
J = 8.7, 0.9 Hz, 2 H), 6.84 (t, J = 7.8 Hz, 1 H), 6.86 (dd, J = 7.8, 1.8
Hz, 1 H), 7.04 (d, J = 7.8 Hz, 1 H), 7.16 (dd, J = 8.7, 1.8 Hz, 1 H),
7.18–7.23 (m, 4 H), 7.34 (d, J = 8.7 Hz, 1 H).
13C NMR: d = 17.01, 104.12, 112.04, 114.03, 115.94, 117.60,
119.45, 121.58, 122.73, 123.10, 128.59, 128.85, 129.52, 131.51,
132.56, 140.16, 141.98, 145.23, 148.00.
(3) (a) Capuano, L.; Mörsdorf, P.; Scheidt, H. Chem. Ber. 1983,
116, 741. (b) Bossio, R.; Marcaccini, S.; Paoli, P.; Pepino,
R.; Polo, C. Synthesis 1991, 999.
Synthesis 2010, No. 4, 666–670 © Thieme Stuttgart · New York

670
K. Kobayashi et al.
PAPER
(4) (a) Kobayashi, K.; Nagato, S.; Kawakita, M.; Morikawa, O.;
Konishi, H. Chem. Lett. 1995, 575. (b) Kobayashi, K.;
Matoba, T.; Irisawa, S.; Matsumoto, T.; Morikawa, O.;
Konishi, H. Chem. Lett. 1998, 551. (c) Kobayashi, K.;
Irisawa, S.; Matoba, T.; Matsumoto, T.; Yoneda, K.;
Morikawa, O.; Konishi, H. Bull. Chem. Soc. Jpn. 2001, 74,
1109. (d) Kobayashi, K.; Takagoshi, K.; Kondo, S.;
Morikawa, O.; Konishi, H. Bull. Chem. Soc. Jpn. 2004, 77,
553. (e) Kobayashi, K.; Izumi, Y.; Hayashi, K.; Morikawa,
O.; Konishi, H. Bull. Chem. Soc. Jpn. 2005, 78, 2171.
(f) Kobayashi, K.; Himei, Y.; Izumi, Y.; Fukamachi, S.;
Morikawa, O.; Konishi, H. Heterocycles 2007, 71, 691.
(5) Ito, Y.; Kobayashi, K.; Seko, N.; Saegusa, T. Bull. Chem.
Soc. Jpn. 1984, 57, 73.
(6) Senier, A.; Shepheard, F. G. J. Chem. Soc. 1909, 95, 1943.
(7) Cinneide, R. O. Nature 1955, 175, 47.
Synthesis 2010, No. 4, 666–670 © Thieme Stuttgart · New York