A facile synthesis of benzofuran derivatives: A useful synthon for preparation of trypsin inhibitor

Article abstract of DOI:10.3987/com-02-s27

Mono-substituted 2-methylbenzo[b]furans were prepared by Claisen rearrangement of corresponding allyl phenyl ethers and subsequent bis(benzonitrile)palladium(II) chloride-mediated cyclization of o-allylphenols.

Full text of DOI:10.3987/com-02-s27

HETEROCYCLES, Vol. 59, No. 1, 2003, pp. 237 - 243, Received, 15th July, 2002
A F ACILE SYNTHESIS OF BENZOFURAN DERIVATIVES: A
USEFUL SYNTHON FOR PREPARATION OF TRYPSIN
INHIBITOR#
Haruo Sekizaki, Kunihiko Itoh, Eiko Toyota, and Kazutaka Tanizawa*
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido,
Ishikari-Tobetsu, Hokkaido 061-0293, Japan
E-mail: tanizawa@hoku-iryo-u.ac.jp
Abstract Mono-substituted 2-methylbenzo[b]furans were prepared by Claisen
rearrangement of corresponding allyl phenyl ethers and subsequent
bis(benzonitrile)palladium(II) chloride-mediated cyclization of o-allylphenols.
Protection of functional groups 1 is one of the most important synthetic technique in the preparative organic
chemistry. In the synthesis of multifunctional molecules the problem often arises that a given functional
group has to be protected from a certain reactions. Of the many functional groups requiring synthetic
manipulation involving protection, one frequently encounter ortho-formylphenol, i.e., salicylaldehyde
residue. The most strategic approach for protection of salicylaldehyde residue seems to be the formation of
benzofuran ring. This benzofuran linkage may be taken as very stable protection for the salicylaldehyde,2
and it was easily converted to salicylaldehyde residue by cleavage of furan ring as shown in the previous
paper.3 Previously, we reported that formation of a very stable chelate composed of salicylaldehyde,
α-amino acid, and metal ion (structure C, Scheme 1).4 The series of Schiff bases chelates were applied to
the design of bio-specific compound, and they were found to be very useful trypsin-inhibitor.5 We are
interested in these trypsin-inhibitors, therefore, we examined the utility of benzofuran derivatives for the
synthesis of various position isomers of salicylaldehyde possessing amidine and guanidine function at the
benzene ring.
# This paper is dedicated to Emeritus Professor Yuichi Kanaoka, Hokkaido University, on the occasion of
his 75th birthday.

In this paper, we report a facile synthesis of benzofuran derivatives (25-32) (Schemes 3 and 4). These
compounds possess the nitrogen-containing groups at various position of benzene ring, and these functional
groups can be converted into the site-specific groups for trypsin such as amidino and guanidino groups. Our
strategy for the preparation of benzofuran derivative by means of palladium(II)-mediated cyclization is
shown in Schemes 3 and 4. The starting material, p-N-Cbz-aminophenol (7), was prepared as previously
reported.6 The isomer, m-N-Cbz-aminophenol (5), was also prepared according to our previous paper 6 as
shown in Scheme 2. Tertrahydropyranylation of m-nitrophenol (1) gave the m-tetrahydropyran-2-yloxy-
nitrobenzene (2). Compound (2) was converted to the m-aminophenol derivative (3), then, the amino
group of 3 was protected with N-(benzyloxycarbonyloxy)succinimide (Cbz-ONSu) to give m-tetrahydro-
pyran-2-yloxy-N-Cbz-aminobenzene (4). Deprotection of 4 gave m-N-Cbz-aminophenol (5) in 54% yield
from 1. The other starting materials, 3-cyanophenol (6), 4-cyanophenol (8), 4-cyanomethylphenol (9), and
2-cyanophenol (1 0), are commercially available.
The key compounds, o-allylphenols (17-24), were prepared from allyl phenyl ethers (11-16) which were
obtained from the corresponding phenols (5-10) and allyl bromide in satisfactory yields. Claisen
rearrangement of allyl m-substituted phenyl ethers (1 1 and 1 2) by refluxing with 1,2-dichlorobenzene for
24-48 h resulted to give a mixture of position isomers as shown in Scheme 3. Claisen rearrangement of
allyl phenyl ethers bearing substituent at para- (1 3-1 5) or ortho-position (1 6), afforded o-allylphenols
(21-2 4) in reasonable yields. o-Allylphenols (1 7-2 4) were cyclized to give corresponding derivatives

(2 5-3 2) by equimolar amount of bis(benzonitrile)palladium(II) chloride, (C6H5CN)2PdCl2, in boiling
benzene. The yields are generally moderate (44-78%).
Finding of the present study will provide a facile mean for the synthesis of benzofuran derivatives from
appropriate o-allylphenols.
EXPERIMENTAL
Melting points were determined on a Yanagimoto melting point apparatus and are uncorrected. IR spectra
1
were taken on a JASCO FT/IR-460Plus. H NMR spectra were recorded on a JEOL JNM-EX 400 (400
MHz) and JEOL LA-300 (300 MHz) spectrometers. Chemical shifts are quoted in parts per million (ppm)
with tetramethyl silane (TMS) as an internal standard. HRMS spectra were recorded using a JEOL
JMS-DX 303 spectrometer. TLC was performed on Merck Silica gel 60F-254. Column chromatography
was carried out on Kieselgel 60 (Merck).
m-Tetrahydropyran-2-yloxynitrobenzene (2)
TsOH·H2O (20 mg) was added to a solution of
m-nitrophenol (1) (13.9 g, 0.1 mol) and 3,4-dihydro-2H-pyran (12.6 g, 0.15 mol) in anhydrous benzene
(50 mL). An exothermic reaction occurred immediately after the addition. After the exothermic reaction
stopped, the reaction mixture was warmed at 50 °C for 1 h. It was diluted with AcOEt (50 mL), washed
successively with 1 M aqueous NaOH, water and saturated brine, dried over anhydrous Na2SO4 and
evaporated in vacuo. The residual oil was passed through a short column of silica gel with benzene.
Compound (2) (18.31 g, 82%) was obtained as a yellow syrup. IR (neat) ν = 2946, 1530, 1351, 1239
1
cm-1. H NMR (CDCl3) δ = 1.58-1.75 (3H, m), 1.87-2.01 (3H, m), 3.62-3.68 (2H, m), 3.81-3.89 (2H,
m), 5.51 (1H, dd, J = 3.1, 3.1 Hz), 7.36 (1H, dd, J = 7.8, 7.8 Hz), 7.84 (1H, dd, J = 7.8, 2.2 Hz), 7.91
(1H, dd, J = 2.2, 2.0 Hz). HRMS: Calcd for C11H13NO4 : 223.0844. Found: 223.0853.
m-Tetrahydropyran-2-yloxyaminobenzene (3) A suspension of 2 (11.15 g, 50 mmol) in EtOH
(250 mL) containing 10% Pd-C was vigorously stirred in an atmosphere of hydrogen at rt for 4 h. The
catalyst was removed by passing the solution through a bed of celite, and the catalyst and celite were
washed with EtOH. The combined solution was concentrated in vacuo, and the residue (crude 3) was used
for the next reaction without purification.
m-Tetrahydropyran-2-yloxy-N-(benzyloxycarbonyl)aminobenzene (4) A solution of crude 3
(from 2, 50 mmol) in CHCl3 (100 mL) was treated with Cbz-ONSu (12.45 g, 50 mmol). The reaction
mixture was stirred at rt for 2 h, then the solution was concentrated to dryness in vacuo. The residual oil
was passed through a short column of silica gel with a mixture of benzene : AcOEt (6 : 1). Compound (4)

(14.39 g, 88%) was obtained as a yellow syrup. IR (neat) ν = 3318, 2946, 1734, 1604, 1221 cm-1. 1H
NMR (CDCl3) δ = 1.54-1.71 (3H, m), 1.79-1.84 (2H, m), 1.92-2.00 (1H, m), 5.17 (2H, s), 5.39 (1H,
dd, J = 3.1, 3.1 Hz), 6.74 (1H, dd, J = 8.1, 2.2 Hz), 6.83 (1H, s), 6.96 (1H, dd, J = 8.1, 8.1 Hz),
7.31-7.38 (5H, m). HRMS: Calcd for C11H13NO4 : 327.1466. Found: 327.1470.
m-N-(Benzyloxycarbonyl)aminophenol (5) A solution of 4 (13.28 g, 40.6 mmol) in MeOH (120
mL) was treated with TsOH·H2O (771 mg, 40.6 mmol). The reaction mixture was refluxed for 1 h, then
evaporated to dryness in vacuo. The residual oil was passed through a short column of silica gel with a
mixture of benzene : AcOEt (6 : 1), and pure 5 (7.40 g, 75%) was obtained by recrystallization from
benzene-AcOEt as colorless needles. mp 129-130 °C. IR (neat) ν = 3373, 1670, 1608, 1548, 1291, 1246
1
cm-1. H NMR (CDCl3) δ = 4.93 (2H, s), 6.39 (1H, br s), 6.60 (1H, dd, J = 7.4, 1.2 Hz), 6.68 (1H, dd,
J = 4.4, 1.2 Hz), 7.11 (1H, J = 8.1 Hz), 7.13 (1H, d, J = 8.1 Hz), 7.33-7.39 (5H, m). Anal. Calcd for
C14H13NO3: C, 69.12; H, 5.39; N, 5.76. Found: C, 69.38; H, 5.41; N, 5.69.
General procedure for the synthesis of allyl ethers (11-16)----Allyl bromide (2.764 g, 20 mmol)
was added to a suspension of phenol derivatives (5-1 0, 10 mmol) and K2CO3 (4.14g, 30 mmol) in acetone
(100 mL) at rt. The reaction mixture was stirred at rt for 24 h, then the precipitate was filtered off, and the
filtrate was evaporated to dryness in vacuo. The residual oil was passed through a short column of silica gel
with benzene : AcOEt (15 : 1 - 1 : 5) to give allyl ether.
Allyl 3 -N-(benzyloxycarbonyl)aminophenyl ether (11): This was obtained in 98% yield (2.773 g)
1
as a slightly yellow syrup. IR (neat) ν = 3327, 1734, 1708, 1606, 1221 cm-1. H NMR (CDCl3) δ = 4.51
(2H, d, J = 5.3 Hz), 5.19 (2H, s), 5.27 (1H, dd, J = 10.3, 1.3 Hz), 5.40 (1H, dd, J = 17.3, 1.3 Hz),
6.05 (1H, m), 6.62 (1H, dd, J = 8.3, 2.5 Hz), 6.70 (1H, br s), 6.85 (1H, d, J = 8.3 Hz), 7.15 (2H, J =
8.3 Hz), 7.35-7.39 (5H, m) . HRMS: Calcd for C17H17NO3: 283.1198. Found: 283.1205.
Allyl 3-cyanophenyl ether (12): This was obtained in 96% yield (1.526 g) as a colorless liquid. IR
(neat) ν = 2230, 1596, 1578, 1290, 1263 cm-1. 1H NMR (CDCl3) δ = 4.55 (1H, dd, J = 1.4, 1.4 Hz),
4.57 (1H, dd, J = 1.4, 1.4 Hz), 5.32 (1H, dd, J = 10.3, 1.5 Hz), 5.42 (1H, ddd, J = 17.0, 2.9, 1.5 Hz),
6.03 (2H, br s, overlap), 7.25 (1H, d, J = 7.3 Hz), 7.36 (1H, dd, J = 7.8, 7.3 Hz). HRMS: Calcd for
C11H13NO4: 159.0684. Found: 159.0703.
Allyl 4 -N-(benzyloxycarbonyl)aminophenyl ether (13): This was obtained in 90% yield (2.547
g) as colorless needles. mp 98-99 °C (recrystallized from benzene-hexane). IR (KBr) ν = 3310, 1702,
1
1537, 1236 cm-1. H NMR (CDCl3) δ = 4.50 (1H, dd, J = 1.4, 1.4 Hz), 4.52 (1H, dd, J = 1.4, 1.4 Hz),
5.19 (2H, s), 5.28 (1H, dd, J = 10.3, 1.4 Hz), 5.39 (1H, dd, J = 15.6, 1.4 Hz), 6.04 (1H, m), 6.56 (1H,
br s), 6.85 (2H, d, J = 9.0 Hz), 7.27 (2H, d, J = 9.0 Hz), 7.35 (5H, m).Anal. Calcd for C17H17NO3: C,
72.07; H, 6.05; N, 4.94. Found: C, 72.01; H, 6.07; N, 4.86.
Allyl 4-cyanophenyl ether (14): This was obtained in 99% yield (1.583 g) as colorless needles. mp
41 °C (recrystallized from hexane). IR (KBr) ν = 2220, 1605, 1507, 1256 cm-1. 1H NMR (CDCl3) δ =
4.58 (1H, dd, J = 1.4, 1.4 Hz), 4.60 (1H, dd, J = 1.4, 1.4 Hz), 5.32 (1H, dd, J = 10.3, 1.4 Hz), 5.43
(1H, dd, J = 15.6, 1.4 Hz), 6.04 (1H, m), 6.96 (2H, d, J = 8.8 Hz), 7.58 (2H, d, J = 8.8 Hz). Anal.
Calcd for C10H9NO: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.54; H, 5.77; N, 8.73.
Allyl 4-cyanomethylphenyl ether (15): This was obtained in 85% yield (1.470 g) as a yellow syrup.
1
IR (neat) ν = 2250, 1613, 1512, 1247 cm-1. H NMR (CDCl3) δ = 3.68 (2H, s), 4.53 (1H, dd, J = 1.5,
1.5 Hz), 4.55 (1H, dd, J = 1.5, 1.5 Hz), 5.29 (1H, dd, J = 10.3, 1.4 Hz), 5.41 (1H, dd, J = 15.6, 1.4
Hz), 6.04 (1H, m), 6.91 (2H, d, J = 8.6 Hz), 7.23 (2H, d, J = 8.6 Hz). HRMS: Calcd for C11H13NO4:

173.0841. Found: 173.0856 .
Allyl 2-cyanophenyl ether (16): This was obtained in 89% yield (1.408 g) as a colorless liquid. IR
1
(neat) ν = 2227, 1599, 1491, 1450, 1290 cm-1. H NMR (CDCl3) δ = 4.65 (1H, dd, J = 1.4, 1.4 Hz),
4.66 (1H, dd, J = 1.4, 1.4 Hz), 5.32 (1H, dd, J = 10.8, 1.4 Hz), 5.48 (1H, dd, J = 17.6, 1.5 Hz), 6.03
(1H, m), 6.96 (1H, d, J = 8.8 Hz), 7.01 (1H, d, J = 7.3 Hz), 7.51 (1H, dd, J = 7.8, 1.5 Hz), 7.54 (1H,
dd, J = 7.8, 1.5 Hz). HRMS: Calcd for C11H13NO4: 159.0684. Found: 159.0689 .
General procedure for the synthesis of Claisen rearrangement products (17-24)----A
solution of allyl ethers (1 1-1 6, 5 mmol) in 1,2-dichlorobenzene (100 mL) was refluxed for 24 - 48 h in an
atmosphere of nitrogen. The reaction mixture was evaporated to dryness in vacuo and the residual oil was
passed through a short column of silica gel with benzene : AcOEt (15 : 1 - 1 : 5) to give allyl phenol.
2-Allyl-3-N-(benzyloxycarbonyl)aminophenol (17): This was isolated in 20% yield (283 mg) as a
1
colorless syrup. IR (neat) ν = 3392, 1704, 1598, 1532, 1470, 1227 cm-1. H NMR (CDCl3) δ = 4.51
(2H, d, J = 5.3 Hz), 5.19 (2H, s), 5.27 (1H, dd, J = 10.3, 1.3 Hz), 5.40 (1H, dd, J = 17.3, 1.3 Hz),
6.05 (1H, m), 6.62 (1H, dd, J = 8.3, 2.5 Hz), 6.70 (1H, br s), 6.85 (1H, d, J = 8.3 Hz), 7.15 (2H, J =
8.3 Hz), 7.35-7.39 (5H, m) . HRMS: Calcd for C11H13NO4: 283.1208. Found: 283.1205.
2-Allyl-5-N-(benzyloxycarbonyl)aminophenol (18): This was isolated in 55% yield (778.3 mg)
as colorless needles. mp 108-109 °C (recrystallized from benzene-hexane). IR (KBr) ν = 3349, 1686,
1
1554, 1247, 1229 cm-1. H NMR (CDCl3) δ = 3.34 (2H, d, J = 6.4 Hz), 5.08 (1H, s), 5.11 (1H, d, J =
5.4 Hz), 5.19 (2H, s), 5.90 (1H, br s), 5.98 (1H, m), 6.66 (1H, dd, J = 8.8, 2.4 Hz), 6.69 (1H, s), 6.99
(1H, d, J = 8.3 Hz), 7.22 (1H, br s), 7.33-7.39 (5H, m). Anal. Calcd for C17H17NO3: C, 72.07; H,
6.05; N, 4.94. Found: C, 71.99; H, 6.23; N, 4.77.
2-Allyl-3-cyanophenol (19): This was isolated in 40% yield (318 mg) as colorless needles. mp
119-120 °C (recrystallized from benzene). IR (KBr) ν = 3324, 2237, 1583, 1465, 1290 cm-1. 1H NMR
(CDCl3) δ = 3.65 (2H, d, J = 6.4 Hz), 5.16 (1H, dd, J = 7.8, 0.9 Hz), 5.19 (1H, s), 5.47 (1H, br s),
5.99 (1H, m), 7.05 (1H, dd, J = 7.3, 1.5 Hz), 7.19-7.26 (2H, m). Anal. Calcd for C10H9NO: C, 75.45;
H, 5.70; N, 8.80. Found: C, 75.45; H,5.77; N, 8.75.
2-Allyl-5-cyanophenol (20): This was isolated in 21% yield (167.1 mg) as colorless fine needles. mp
118-119 °C (recrystallized from benzene-hexane). IR (KBr) ν = 3328, 2238, 1583, 1465, 1290 cm-1. 1H
NMR (CDCl3) δ = 3.65 (2H, dd, J = 6.3, 1.4 Hz), 5.13 (1H, dd, J = 1.5, 1.5 Hz), 5.18 (1H, dd, J = 1.5,
1.5 Hz), 5.95 (1H m), 6.03 (1H, br s), 7.05 (1H, d, J = 7.4 Hz), 7.12 (1H, d, J = 7.4 Hz), 7.23 (1H, s).
Anal. Calcd for C10H9NO: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.45; H, 5.77; N, 8.75.
2-Allyl-4-N-(benzyloxycarbonyl)aminophenol (21): This was obtained in 75% yield (1.061 g) as
colorless fine needles. mp 84-85°C (recrystallized from benzene-hexane). IR (KBr) ν = 3369, 3298, 1657,
1
1542, 1245 cm-1. H NMR (CDCl3) δ = 3.37 (2H, d, J = 6.3 Hz), 5.14 (2H, dd, J = 13.7, 1.5 Hz), 5.18
(2H, s), 5.98 (1H, m), 652 (1H, br s), 6.73 (2H, d, J = 8.8 Hz), 7.09 (2H, d, J = 8.0 Hz), 7.26 (1H, br
s), 7.38 (5H, m). Anal. Calcd for C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 72.00; H, 6.13;
N, 4.74.
2-Allyl-4-cyanophenol (22): This was obtained in 73% yield (580.4 mg) as clorless needles. mp
83-84 °C (recrystallized from benzene-hexane). IR (KBr) ν = 3245, 2236, 1601, 1283 cm-1. 1H NMR
(CDCl3) δ = 3.40 (2H, d, J = 6.3 Hz), 5.14 (1H, dd, J = 17.1, 1.5 Hz), 5.19 (1H, dd, J = 10.3, 1.5 Hz),
5.98 (1H, m), 6.80 (1H, br s), 6.90 (1H, d, J = 8.0 Hz), 7.42 (1H, d, J = 8.0 Hz), 7.43 (1H, s). Anal.
Calcd for C10H9NO: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.36; H, 5.74; N, 8.70.

2-Allyl-4-cyanomethylphenol (23): This was obtained in 84% yield (726.6 mg) as a slightly yellow
1
syrup. IR (neat) ν = 3389, 2258, 1511, 1439 cm-1. H NMR (CDCl3) δ = 3.40 (2H, d, J = 6.3 Hz), 3.66
(2H, s), 5.14 (1H, dd, J = 9.8, 1.5 Hz), 5.18 (1H, dd, J = 1.5, 1.5 Hz), 5.23 (1H, s), 6.00 (1H, m),
6.80 (1H, dd, J =8.8, 2.0 Hz) 7.05 (1H, s), 7.06 (1H, d, J = 8.8, 2.4 Hz). HRMS: Calcd for C11H13NO4:
173.0841. Found: 173.0853 .
2-Allyl-6-cyanophenol (24): This was obtained in 83% yield (658.3 mg) as colorless plates. mp
1
38-39 °C (recrystallized from hexane). IR (KBr) ν = 3293, 2239, 1461, 1210 cm-1. H NMR (CDCl3) δ =
3.44 (2H, d, J = 6.3 Hz), 5.18 (1H, dd, J = 15.4, 1.5 Hz), 5.20 (1H, dd, J = 2.0, 1.5 Hz), 5.98 (1H, m),
6.95 (1H, dd, J = 7.8, 7.8 Hz) 7.34 (1H, dd, J = 7.8, 2.4 Hz), 7.40 (1H, dd, J = 7.8, 2.4 Hz). Anal.
Calcd for C10H9NO: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.49; H, 5.80; N, 8.84.
General procedure for the synthesis of the benzofurans (25-32)----Bis(benzonitrile)-
palladium(II) chloride (384 mg, 1 mmol) was added to a solution of 2-allylphenols (1 7-2 4, 1 mmol) in
anhydrous benzene (50 mL), and the mixture was refluxed for 2 h in an atmosphere of nitrogen. The
inorganic precipitate was removed by passing the solution through a bed of celite, and the filtrate was
evaporated to dryness in vacuo and the residual oil was passed through a short column of silica gel with
benzene or mixture of benzene : AcOEt (6 : 1) to give benzofuran.
4 -N-(Benzyloxycarbonyl)amino-2-methylbenzo[b]furan (25): This was obtained in 60% yield
(168.6 mg) as colorless needles. mp 110-111°C (recrystallized from hexane). IR (KBr) ν = 3316, 1692,
1
1533, 1267, 1059 cm-1. H NMR (CDCl3) δ = 2.57 (3H, s), 5.44 (2H, s), 6.41 (1H, d, J = 0.9 Hz), 7.05
(1H, dd, J = 7.8, 7.8 Hz), 7.35-7.54 (5H, m), 7.69 (1H, dd, J = 7.8, 0.6 Hz). Anal. Calcd for
C17H15NO3: C, 72.58; H, 5.37; N, 4.98. Found: C, 72.55; H, 5.46; N, 4.83.
6 -N-(Benzyloxycarbonyl)amino-2-methylbenzo[b]furan (26): This was obtained in 44% yield
(123.7 mg) as colorless fine needles. mp 119-120 °C (recrystallized from benzene-hexane). IR (KBr) ν =
1
3349, 1707, 1580, 1453, 1327, 1286 cm-1. H NMR (CDCl3) δ = 2.43 (3H, s), 5.21 (2H, s), 6.30 (1H,
s), 6.72 (1H, br s), 7.00 (1H, dd, J = 8.3, 1.8 Hz), 7.32-7.43 (7H, m). HRMS: Calcd for C17H15NO3:
281.1052. Found: 281.1057. Anal. Calcd for C17H15NO3: C, 72.58; H, 5.37; N, 4.98. Found: C,
73.06; H, 5.50; N, 4.83.
4-Cyano-2-methylbenzo[b]furan (27): This was obtained in 58% yield (91.1 mg) as colorless
1
needles. mp 40-41 °C (sublimed at room temperature). IR (KBr) ν = 2220, 1603, 1430, 1260 cm-1. H
NMR (CDCl3) δ = 2.44 (3H, s), 6.54 (1H, dd, J = 1.1, 1.1 Hz), 7.18 (1H, dd, J = 8.2, 5.7 Hz), 7.43
(1H, dd, J =7.7, 1.1 Hz) 7.53 (1H, d, J = 8.2 Hz). HRMS: Calcd for C10H7NO: 157.0528. Found:
157.0514.
6-Cyano-2-methylbenzo[b]furan (28): This was obtained in 49% yield (76.9 mg) as colorless
needles. mp 66-67 °C (recrystallized from benzene-hexane). IR (KBr) ν = 2221, 1602, 1425, 1261, 1195
1
cm-1. H NMR (CDCl3) δ = 2.42 (3H, s), 6.38 (1H, s), 7.37 (1H, dd, J = 7.8, 1.2 Hz), 7.45 (1H, d, J
=7.8 Hz) 7.60 (1H, d, J = 1.2 Hz). HRMS: Calcd for C10H7NO: 157.0528. Found: 157.0515.
5 -N-(Benzyloxycarbonyl)amino-2-methylbenzo[b]furan (29): This was obtained in 45% yield
(126.5 mg) as colorless needles. mp 105-106 °C (recrystallized from benzene-hexane). IR (KBr) ν = 3313,
1
1701, 1536, 1240 cm-1. H NMR (CDCl3) δ = 2.42 (3H, d, J = 1.0 Hz), 6.31 (1H, s), 6.72 (1H, br s),
7.06 (1H, dd, J = 8.8, 2.0 Hz), 7.24-7.56 (7H, m). Anal. Calcd for C17H25NO3: C, 72.58; H, 5.37; N,
4.98. Found: C, 72.59; H, 5.46; N, 4.78.
5-Cyano-2-methylbenzo[b]furan (30): This was obtained in 53% yield (83.2 mg) as colorless

needles. mp 73-74°C (recrystallized from hexane) (lit.,7 76-78 °C).
5-Cyanomethyl-2-methylbenzo[b]furan (31): This was obtained in 46% yield (78.7 mg) as a
colorless liquid. IR (neat) ν = 2251, 1608, 1493 cm-1. 1H NMR (CDCl3) δ = 2.46 (3H, s), 6.38 (2H, s),
6.36 (1H, s), 7.10 (1H, dd, J = 8.8, 2.8 Hz), 7.37 (1H, d, J = 8.6 Hz), 7.43 (1H, d, J = 1.8 Hz).
HRMS: Calcd for C11H13NO4: 171.0684. Found: 171.0685.
7-Cyano-2-methylbenzo[b]furan (32): This was obtained in 78% yield (123.3 mg) as colorless
1
needles. mp78°C (recrystallized from hexane). IR (KBr) ν = 2228, 1605, 1423 cm-1. H NMR (CDCl3) δ
= 2.53 (3H, s), 6.63 (1H, s), 7.25 (1H, dd, J = 7.8, 7.3 Hz), 7.49 (1H, d, J = 7.8 Hz), 7.69 (1H, d, J
=7.3 Hz). HRMS: Calcd for C10H7NO: 157.0528. Found: 157.0538. Anal. Calcd for C10H7NO: C, 76.14;
H, 4.49; N, 8.91. Found: C, 75.67; H, 4.46; N, 8.64.
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