A short synthesis of phenanthro[2,3-d]imidazoles from dehydroabietic acid. Application of the methodology as a convenient route to benzimidazoles

Article abstract of DOI:10.1016/S0040-4020(00)01158-3

Methyl cis-deisopropyldehydroabietate was selectively nitrated at the 12-position by reaction with 'claycop', a montmorillonite clay impregnated with copper(II) nitrate. The 12-nitro compound was reduced to the corresponding amine and this was subjected to a combined acylation and ortho nitration. The compounds so produced were further converted into octahydro-1H-phenanthro[2,3-d]imidazoles by reductive cyclization. The same acylation-ortho nitration methodology was shown to provide a short synthesis of 2-substituted benzimidazoles from aniline.

Full text of DOI:10.1016/S0040-4020(00)01158-3

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1793±1799
A short synthesis of phenanthro[2,3-d]imidazoles from
dehydroabietic acid. Application of the methodology as a
convenient route to benzimidazoles
a,b a,p
Tatiana Fonseca, Barbara Gigante and Thomas L. Gilchrist
b
Â
aInstituto Nacional de Engenharia e Tecnologia Industrial, DTIQ, Estrada do PacËo do Lumiar, 1649-038 Lisboa, Portugal
bDepartment of Chemistry, The University of Liverpool, Liverpool L69 7ZD, UK
Received 27 September 2000; revised 10 November 2000; accepted 8 December 2000
AbstractÐMethyl cis-deisopropyldehydroabietate was selectively nitrated at the 12-position by reaction with `claycop', a montmorillonite
clay impregnated with copper(II) nitrate. The 12-nitro compound was reduced to the corresponding amine and this was subjected to a
combined acylation and ortho nitration. The compounds so produced were further converted into octahydro-1H-phenanthro[2,3-d]imida-
zoles by reductive cyclization. The same acylation-ortho nitration methodology was shown to provide a short synthesis of 2-substituted
benzimidazoles from aniline. q 2001 Elsevier Science Ltd. All rights reserved.
Dehydroabietic acid 1, the main constituent of dis-
proportionated rosin, and several of its derivatives show
antibacterial or antifungal activity.1 Methyl dehydroabietate
is readily transformed into methyl cis-deisopropyldehydro-
abietate 2 by reaction with aluminium trichloride2 and
this compound provides a convenient starting material for
the construction of other derivatives. Some of these
derivatives lacking the isopropyl group are also anti-
microbial agents.3 The discovery that `claycop', a mont-
morillonite clay impregnated with copper(II) nitrate, could
act as a selective nitrating agent for activated aromatic
compounds4 led us to investigate the selective nitration of
the ester 2.5 It was found that the selectivity for the forma-
tion of the 12-nitro derivative 3 over the 13-nitro and 14-
nitro isomers was signi®cantly improved when this reagent
was used.
The aim of the present work was to construct imidazoles
fused to the aromatic ring of the dehydroabietic acid
skeleton with this 12-nitro derivative 3 as the starting
material. Benzimidazoles are known to have diverse bio-
logical activity and, by combining the imidazole ring system
with the dehydroabietic acid skeleton, there seemed a good
possibility that the new compounds would show useful anti-
bacterial or antifungal properties. An ef®cient route to a
series of phenanthro[2,3-d]imidazole derivatives having
the general structure 4 has been developed. The key step
is a one pot acylation and ortho nitration procedure starting
from the amine 5 (Scheme 1). This procedure had
previously been carried out successfully with aniline and
acetic anhydride4 and we have now shown that this is also
a general and convenient method for the synthesis of benz-
imidazoles from aniline (Scheme 2).
Keywords: diterpenes; resin acids; benzimidazoles.
Corresponding author. Tel.: 1351-217-165-141; fax: 1351-217-168-100; e-mail: barbara.gigante@mail.ineti.pt
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01158-3

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T. Fonseca et al. / Tetrahedron 57 (2001) 1793±1799
Scheme 1.
Scheme 2.
1. Phenanthro[2,3-d]benzimidazole derivatives
Preliminary assays have shown that the imidazoles 4
possess both antimicrobial and antifungal activity. These
results will be reported separately.
The nitroarene 3 was obtained in 43% yield as a yellow
crystalline solid from methyl cis-deisopropyldehydro-
abietate 2 by nitration with `claycop' followed by recrystal-
lization from methanol. It was reduced in high yield to the
amine 5 by catalytic hydrogenation. The combined acylation
and nitration of the amine 5 was carried out by adding the
amine to a cooled suspension of `claycop' and the appropriate
carboxylic acid anhydride in carbon tetrachloride. By this
means three 12-acylamino-13-nitro- compounds 6a±c were
prepared and isolated in 60±70% yield. The formamide 6d
was prepared (59%) by a slight modi®cation of the general
procedure. The procedure did not succeed when benzoic
anhydride was used so the benzamide 6e was prepared in
two steps, and in good overall yield, by benzoylation of the
amine 5 to give the amide 7 followed by nitration.
2. Benzimidazoles
Having established this route as an ef®cient method for the
preparation of the phenanthro[2,3-d]imidazoles 4 the
methodology was brie¯y applied to the conversion of
aniline into 2-substituted benzimidazoles (Scheme 2). The
2-nitro-N-acylanilines 9a±e were prepared in one step by
the reaction with the appropriate acid anhydride and `clay-
cop'. This method worked well with acetic, butyric, acetic-
formic and benzoic anhydrides but the yield of the amide 9c
was low (40%) in the reaction with tri¯uoroacetic anhydride
because the major product (52%) was 4-nitrotri¯uoro-
acetanilide. These amides were then converted into benzi-
midazoles 11 by either of the two procedures described
above for compounds 4. The yields were usually higher
when the two step procedure, involving isolation of the
amines 10 and subsequent cyclization, was used although
benzimidazole 11d and 2-tri¯uoromethylbenzimidazole 11c
were prepared in good yield by the one step method.
2-Nitro-N-acylanilines are well established as intermediates
in the synthesis of 2-substituted benzimidazoles.6 The reac-
tion sequence is reduction of the nitro group to an amino
group followed by cyclodehydration. With the nitro
compounds 6 catalytic hydrogenation of the nitro group
required forcing conditions. The reactions were best carried
out under a pressure of 50±100 psi over a palladium
catalyst. When the hydrogenation was performed at rt the
corresponding amines 8 were isolated and these were then
cyclized to the imidazoles 4 by heating in a mixture of
xylenes and acetic acid. Alternatively when the catalytic
hydrogenation was carried out at 1208C and in the presence
of a catalytic amount of montmorillonite clay (K10) as an
acid catalyst, the imidazoles 4 could be obtained directly as
the major or exclusive products.
3. Experimental
3.1. Materials and methods
All reagents were of analytical grade, dried and puri®ed
when necessary. Dehydroabietic acid 1 was obtained from
commercially disproportionated rosin and was puri®ed by

T. Fonseca et al. / Tetrahedron 57 (2001) 1793±1799
1795
repeated crystallization of the ethanolamine salt.7 Methyl
dehydroabietate8 was prepared from the acid by reaction
with diazomethane. `Claycop' was prepared by impregna-
tion of an acidic montmorillonite clay (K10), commercially
available, with cupric nitrate, according to a published
procedure.9 Light petroleum refers to the fraction bp
40±608C.
(C-4b) and 179.5 (COOCH3); MS m/z 272 [M]1 (12%),
257 (17%) and 197 (100%). Anal. Calcd for C18H24O2 C
79.37, H 8.88; found C 79.13, H 8.87%.
3.2.2. Methyl (1R,4aR,10aR)-1,4a-dimethyl-6-nitro-1,2,3,
4,4a,9,10,10a-octahydrophenanthrene-1-carboxylate 3.
The ester 2 (4.01 g, 14.7 mmol) was added to a suspension
of `claycop' (3.94 g, 17.1 mmol) in carbon tetrachloride
(23 mL) and acetic anhydride (12.5 mL), in an ice-bath.
The mixture was vigorously stirred at rt and the reaction
followed by TLC, until completion, and then ®ltered. The
®lter cake was washed with diethyl ether and the combined
organic extracts were washed with water followed by aq.
sodium hydrogen carbonate, dried over anhydrous sodium
sulfate, ®ltered and concentrated under reduced pressure
(5.29 g). Analysis by GC showed 3 (51%), 7-nitrophenan-
threne (28%) and 8-nitrophenanthrene (19%). By recrystal-
lization compound 3 (2.0 g, 6.3 mmol, 43%) was isolated as
yellow crystals, mp 108±1108C (from methanol) (lit.5 109±
1108C); FT-IR (KBr) nmax 1726, 1517, 1346 and
1H NMR spectra were recorded at 300 MHz, and 13C NMR
spectra were recorded at 75.5 MHz, on a Varian Gemini 300
instrument. Mass spectra were recorded on a VG micromass
7070E instrument under electron impact at 70 eV. Micro-
analyses were performed in the University of Liverpool
microanalysis laboratory.
3.2. Nomenclature
Compounds derived from dehydroabietic acid have been
named systematically in the Section 3 as derivatives of
phenanthrene (A) or of phenanthro[2,3-d]imidazole (B).
The systematic numbering of the two ring systems is shown.
1
1137 cm21; H NMR (CDCl3, 300 MHz) d 1.07 (3H, s),
1.26 (3H, s), 1.24±1.28 (1H, m), 1.48±1.69 (3H, m);
1.78±1.88 (2H, m), 2.02±2.17 (2H, m), 2.39 (1H, dd,
Jˆ10.4 and 3.3 Hz), 2.93±2.97 (2H, m), 3.69 (3H, s), 7.18
(1H, d, Jˆ8.5 , 8-H), 7.92 (1H, dd, Jˆ8.4 and 2.3 Hz, 7-H)
and 8.17 (1H, d, Jˆ2.3 Hz, 5-H); 13C NMR (CDCl3,
75.5 MHz) d 19.4, 19.6, 25.6, 27.7, 30.3, 32.2, 36.8, 38.9,
45.1, 45.2, 51.8, 120.4, 121.6, 129.7, 144.2, 146.8, 148.0
and 179.2; MS m/z 317 [M]1(6%), 300 (5%), 242 (100%)
and 176 (35%). Anal. Calcd for C18H23NO4 C 68.12, H 7.30,
N 4.41; found C 68.28, H 7.32, N 4.34%.
3.2.3. Methyl (1R,4aR,10aR)-6-amino-1,4a-dimethyl-1,2,
3,4,4a,9,10,10a-octahydrophenanthrene-1-carboxylate
5. A mixture of the nitro compound 3 (2.20 g, 6.94 mmol)
and Pd/C 5% (238 mg) in ethanol (66.5 mL) was stirred in a
pressure reactor at rt under H2 (100 psi). The reaction was
followed by TLC and at the end the reaction mixture was
®ltered over Celite and the catalyst washed with dichloro-
methane. After the solvent was evaporated under reduced
pressure, the amine 5 (2.00 g, 6.66 mmol, 96%) was
obtained as white crystals, mp 115±1178C (from ethanol);
IR (KBr) nmax 3465, 3372, 1708, 1629, 1257 and
3.2.1. Methyl (1R,4aR,10aR)-1,4a-dimethyl-1,2,3,4,4a,9,
10,10a-octahydro-phenanthrene-1-carboxylate (methyl
cis-deisopropyldehydroabietate) 2. Aluminium trichloride
(94.43 g, 0.71 mol) was added carefully to a solution of
methyl dehydroabietate (42 g, 0.12 mol) in toluene
(500 mL), with vigorous stirring, under N2, at rt. The reac-
tion was followed by GC analysis. After the reaction was
complete (4.5 h) water and sodium hydroxide pellets were
added to the reaction mixture, maintained in an ice bath. The
separated organic layer was washed with water and dried
with anhydrous sodium sulfate. The aqueous layer was
extracted with diethyl ether, washed with water and dried
with anhydrous sodium sulfate. The combined organic
layers were evaporated to dryness. The residue obtained
was dissolved in light petroleum and treated with charcoal
and ®ltered after 24 h. The solution was dried and evapo-
rated to leave a yellow gum. By recrystallization, methyl
cis-deisopropyldehydroabietate 2 was obtained as colour-
less crystals, mp 90±928C (from methanol) (lit.2 93±
1
1192 cm21; H NMR (CDCl3, 300 MHz) d 1.07 (3H, s),
1.17 (3H, s), 1.18±1.20 (1H, m), 1.43±1.61 (3H, m);
1.72±1.83 (2H, m), 1.94±2.03 (2H, m), 2.29 (1H, dd,
Jˆ10.6 and 3.6 Hz), 2.72±2.77 (2H, m), 3.40 (2H, brs),
3.67 (3H, s), 6.46 (1H, dd, Jˆ8.0 and 2.4 Hz), 6.60 (1H,
d, Jˆ2.4 Hz) and 6.82 (1H, d, Jˆ8.1 Hz); 13C NMR (CDCl3,
75.5 MHz) d 19.5, 20.2, 25.7, 27.5, 29.3, 32.2, 36.6, 38.4,
45.1, 45.9, 51.5, 112.9, 113.3, 126.4, 129.5, 144.2, 147.2
and 179.8; MS m/z 287 [M]1(70%), 272 (5%), 228 (4%)
and 212 (100%). Anal. Calcd for C18H25NO2 C 75.22, H
8.77, N 4.87; found C 74.99, H 8.88, N 4.79%.
1
948C); IR (Nujol) nmax 1721 and 1176 cm21; H NMR
(CDCl3, 300 MHz) d 1.09 (3H, s, 1-Me), 1.21 (3H, s, 4a-
Me), 1.20±1.22 (1H, m, 2-Ha), 1.50±1.66 (3H, m; 4-Ha,
3-Hb and 10-Hb); 1.75±1.82 (2H, m, 4-Hb and 3-Ha),
1.99±2.04 (2H, m, 2-Hb and 10-Ha), 2.35 (1H, dd,
Jˆ11.1 Hz, 10a-H), 2.84±2.89 (2H, m, 2£9-H), 3.68 (3H,
s, COOCH3), 7.02±7.16 (3H, m; 6-H, 7-H and 8-H) and 7.27
(1H, d, Jˆ7.2 Hz, 5-H); 13C NMR (CDCl3, 75.5 MHz) d
19.7 (C-3), 20.1 (C-10), 26.0 (C-1-Me), 27.5 (C-4a-Me),
30.3 (C-9), 32.2 (C-2), 36.8 (C-4), 38.6 (C-4a), 45.4
(C-1), 46.0 (C-10a), 51.6 (COOCH3), 125.3 (C-5), 125.9
(C-6), 126.2 (C-7), 128.7 (C-8), 136.1 (C-8a), 146.3
3.2.4. Methyl (1R,4aR,10aR)-6-acetamido-1,4a-dimethyl-
7-nitro-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-
carboxylate 6a. The amine 5 (213 mg, 0.75 mmol) was
added to a suspension of `claycop' (350 mg, 1.53 mmol)
in carbon tetrachloride (2.5 mL) and acetic anhydride
(0.9 mL, 9.38 mmol) with vigorous stirring, in an ice-bath.
The reaction mixture was warmed to rt, and the reaction
followed by TLC. At the end (1.5 h), the `claycop' was

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T. Fonseca et al. / Tetrahedron 57 (2001) 1793±1799
®ltered off and the ®lter cake washed with diethyl ether. The
organic phases were washed with water followed by sodium
hydrogen carbonate and dried over anhydrous sodium sul-
fate. After evaporation of the solvent an orange residue
(372 mg) was obtained that was puri®ed by silica column
chromatography with light petroleum±ethyl acetate (6:4) as
eluent. After recrystallization, yellow crystals of the acet-
amide 6a (160 mg, 0.51 mmol, 68%) were obtained, mp
101.5±103.58C (from light petroleum); IR (KBr) nmax
120.1, 125.8, 129.6, 134.4, 134.6, 155.1, 156.7 and 178.9;
MS m/z 428 [M]1 (10%), 353 (60%), 305 (52%), 287 (31%),
69 (100%), 55 (82%) and 41 (99%). HRMS: Calcd for
C20H23F3N2O5 428.15588, found 428.15516.
3.2.7. Methyl (1R,4aR,10aR)-1,4a-dimethyl-6-formami-
do-7-nitro-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-
1-carboxylate 6d. Acetic-formic anhydride was generated
under N2 by the dropwise addition of 98% formic acid
(0.14 mL, 3.58 mmol) to acetic anhydride (0.28 mL,
2.91 mmol) maintained at 08C followed by gentle heating
(50±608C, 2 h). The reaction mixture was cooled to rt and
carbon tetrachloride (5 mL) was added. The amine 5
(296 mg, 1.03 mmol) in carbon tetrachloride (5 mL) was
added dropwise to the reaction mixture. After checking
that the amine had been consumed (TLC), `claycop'
(592.8 mg, 2.62 mmol) followed by acetic anhydride
(1.6 mL, 16.7 mmol) were added. The reaction was
complete in 2.25 h. After workup as for amide 6a the
solid residue (385 mg) was puri®ed by silica column chro-
matography using light petroleum ether±ethyl acetate (6:4)
as eluent. After recrystallization, yellow crystals of the
amide 6d (219 mg, 0.60 mmol, 59%) were obtained, mp
127.9±1308C (from light petroleum±diethyl ether); IR
(®lm) nmax 3358, 1724, 1618, 1578, 1502, 1337, 1254,
1
3378, 1726, 1701, 1655, 1579 and 1339 cm21; H NMR
(CDCl3, 300 MHz) d 1.05 (3H, s), 1.24 (3H, s), 1.23±1.25
(1H, m), 1.54±1.62 (3H, m); 1.81±1.86 (2H, m), 1.99±2.13
(2H, m), 2.27 (3H, s), 2.37 (1H, dd, Jˆ8.0 and 3.3 Hz),
2.86±2.91 (2H, m), 3.70 (3H, s), 7.91 (1H, s), 8.74 (1H, s)
and 10.21 (1H, s); 13C NMR (CDCl3, 75.5 MHz) d 19.3,
19.8, 25.2, 25.6, 27.7, 29.1, 32.5, 36.4, 39.6, 45.3, 51.8,
120.1, 125.3, 132.3, 132.7, 134.1, 156.1, 169.1 and 179.1;
MS m/z 374 [M]1(33%), 332 (53%), 328 (59%), 317 (36%),
299 (14%), 257 (55%), 59 (25%) and 43 (100%). Anal.
Calcd for C20H26N2O5 C 64.16, H 7.00, N 7.48; found C
64.09, H 7.02, N 7.47%.
3.2.5. Methyl (1R,4aR,10aR)-6-butyramido-1,4a-dimethyl-
7-nitro-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-
carboxylate 6b. Under the conditions described for the
preparation of the amide 6a, the amine 5 (200 mg,
0.70 mmol), `claycop' (584 mg, 2.6 mmol), butyric
anhydride (0.8 mL, 4.88 mmol) and carbon tetrachloride
(2.5 mL) gave, after 3.5 h, an oil (314 mg) that was puri®ed
by silica chromatography using light petroleum±ethyl
acetate (8:2) as eluent. The amide 6b was obtained as a
yellow oil (169 mg, 0.42 mmol, 60%), IR (®lm) nmax
3369, 1727, 1620, 1579, 1503, 1335, 1252, and
1
1137 and 733 21; H NMR (CDCl3, 300 MHz) d 1.06 (3H,
s), 1.25 (3H, s), 1.18±1.29 (1H, m), 1.50±1.66 (3H, m),
1.78±1.85 (2H, m), 1.91±2.05 (2H, m), 2.38 (1H, dd,
Jˆ10.0 and 3.6 Hz), 2.87±2.91 (2H, m), 3.70 (3H, s), 7.93
(1H, s), 8.55 (1H, s), 8.76 (1H, s) and 10.18 (1H, s); 13C
NMR (CDCl3, 75.5 MHz) d 19.4, 19.8, 25.4, 27.6, 29.2,
32.3, 36.4, 39.6, 45.3, 51.8, 120.7, 125.5, 131.5, 133.0,
134.0, 156.1, 159.4 and 179.1; MS m/z 360 [M]1 (32%),
345 (3%), 285 (100%), 173 (91%), 115 (67%) and 41 (77%).
Anal. Calcd for C19H24N2O5 C 63.45, H 6.69, N 7.74; found
C 63.60, H 6.95, N 7.56%.
1
1136 cm21; H NMR (CDCl3, 300 MHz) d 1.00 (3H, t,
Jˆ7.3 Hz), 1.06 (3H, s), 1.24 (3H, s), 1.19±1.29 (1H, m),
1.50±1.66 (3H, m), 1.72±1.84 (4H, m), 1.98±2.11 (2H, m),
2.36 (1H, dd, Jˆ11.4 and 3.6 Hz), 2.45 (2H, t, Jˆ7.3 Hz),
2.83±2.85 (2H, m), 3.69 (3H, s), 7.90 (1H, s), 8.77 (1H, s)
and 10.25 (1H, s); 13C NMR (CDCl3, 75.5 MHz) d 13.7,
18.7, 19.3, 19.7, 25.4, 27.5, 29.2, 32.2, 36.3, 39.5, 40.4,
45.1, 45.3, 51.8, 120.0, 125.2, 132.0, 132.6, 133.8, 156.1,
172.1 and 179.1; MS m/z 402 [M]1(23%), 356 (67%), 332
(100%), 317 (21%), 257 (60%), 71 (54%) and 43 (77%).
HRMS: Calcd for C22H30N2O5 402.21545; found
402.21490.
3.2.8. Methyl (1R,4aR,10aR)-6-benzamido-1,4a-dimethyl-
7-nitro-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-
carboxylate 6e. (a) Benzoylation of the Amine 5. Benzoyl
chloride (0.3 mL, 2.30 mmol), the amine 5 (625 mg,
2.13 mmol) and N,N-diisopropylethylamine (0.27 mL,
2.84 mmol) in dry diethyl ether (52 mL) gave methyl
(1R,4aR,10aR)-6-benzamido-1,4a-dimethyl-1,2,3,4,4a,9,10,
10a-octahydrophenanthrene-1-carboxylate
7
(723 mg,
1.85 mmol, 87%) as a white solid, mp 165±1678C (from
heptane±diethyl ether); IR nmax 3328, 2943, 1725, 1649,
3.2.6. Methyl (1R,4aR,10aR)-1,4a-dimethyl-7-nitro-1,2,
3,4,4a,9,10,10a-octahydro-6-tri¯uoroacetamidophenan-
threne-1-carboxylate 6c. Under the conditions described
for the amide 6a, the amine 5 (202 mg, 0.71 mmol), `clay-
cop' (255 mg, 1.11 mmol), tri¯uoroacetic anhydride
(0.5 mL, 3.58 mmol) and carbon tetrachloride (2.5 mL)
gave, after 1 h, an oil (399 mg) that was puri®ed by silica
column chromatography using light petroleum±ethyl ace-
tate (8:2) as eluent. The amide 6c was obtained as a yellow
oil (213 mg, 0.49 mmol, 70%); IR (Nujol) nmax 3315, 1732,
1
1311 and 730 cm21; H NMR (CDCl3, 300 MHz) d 1.08
(3H, s), 1.25 (3H, s), 1.24±1.30 (1H, m), 1.48±1.65 (3H,
m), 1.74±1.84 (2H, m), 1.98±2.09 (2H, m), 2.34 (1H, dd,
Jˆ10.4 and 3.3 Hz), 2.82±2.86 (2H, m), 3.68 (3H, s), 7.03
(1H, d, Jˆ8.1 Hz), 7.36 (1H, dd, Jˆ8.1 and 2.1 Hz), 7.43±
7.53 (3H, m), 7.55 (1H, d, Jˆ2.1 Hz), 7.83 (1H, brs) and
7.86 (2H, dd, Jˆ7.0 and 1.5 Hz); 13C NMR (CDCl3,
75.5 MHz) d 19.6, 20.1, 25.7, 27.7, 29.7, 32.3, 36.7, 38.7,
45.3, 45.8, 51.6, 117.9, 118.2, 127.0, 128.8, 129.3, 131.7,
132.7, 135.3, 135.9, 147.1, 165.7 and 179.6; MS m/z 391
[M]1 (30%), 376 (9%), 316 (38%), 105 (100%) and 77
(55%). Anal. Calcd for C25H29NO3 C 76.70, H 7.47, N
3.58; found C 76.96, H 7.58, N 3.42%.
1
1619, 1592, 1510, 1345, 1301, 1252, and 1141 cm21; H
NMR (CDCl3, 300 MHz) d 1.07 (3H, s), 1.26 (3H, s),
1.23±1.29 (1H, m), 1.51±1.67 (3H, m), 1.76±1.87 (2H,
m), 2.00±2.15 (2H, m), 2.39 (1H, dd, Jˆ10.3 and 3.6 Hz),
2.89±2.94 (2H, m), 3.70 (3H, s), 7.99 (1H, s), 8.67 (1H, s)
and 11.30 (1H, s); 13C NMR (CDCl3, 75.5 MHz) d 19.5,
19.7, 25.6, 27.4, 29.4, 32.0, 36.4, 39.6, 45.1, 45.2, 51.9,
(b) Nitration. By the procedure used for the amide 6a, the
amide
7
(150 mg, 0.38 mmol), `claycop' (142 mg,

T. Fonseca et al. / Tetrahedron 57 (2001) 1793±1799
1797
0.62 mmol), acetic anhydride (0.8 mL, 8.34 mmol), and
carbon tetrachloride (2.5 mL) gave after 0.5 h, yellow
crystals of the amide 6e (160 mg, 0.366 mmol, 96%), mp
161±1628C (from diethyl ether); IR nmax 3364, 1725, 1684,
described for reduction of the nitroamide 6a, the nitroamide
6b (53 mg, 0.13 mmol) was reduced over Pd/C 5% (21 mg)
in ethanol (5 mL) under H2 (100 psi) at rt for 4 h. The
residue obtained (65 mg) was puri®ed by silica column
chromatography using dichloromethane±methanol (24:1);
the amine 8b was isolated as a white foam (50 mg,
0.125 mmol, 96%); IR nmax 3345, 1724, 1660, 1651, 1515,
1
1580, 1501, 1335, 1259, 1136 and 732 cm21; H NMR
(CDCl3, 300 MHz) d 1.07 (3H, s), 1.18±1.24 (1H, m),
1.30 (3H, s), 1.55±1.71 (3H, m), 1.83±1.91 (2H, m),
2.00±2.15 (2H, m), 2.40 (1H, dd, Jˆ10.0 and 3.6 Hz),
2.88±2.93 (2H, m), 3.70 (3H, s), 7.50±7.62 (3H, m), 7.98
(1H, s), 7.98±8.00 (2H, m), 8.99 (1H, s) and 11.24 (1H, s);
13C NMR (CDCl3, 75.5 MHz) d 19.4, 19.8, 25.3, 27.8, 29.2,
32.4, 36.5, 39.7, 45.4, 51.8, 120.0, 125.5, 127.3, 129.1,
132.5, 133.1, 134.2, 134.4, 156.4, 165.9 and 179.2; MS
m/z 436 [M]1 (8%), 390 (37%) and 105 (100%). Anal.
Calcd for C25H28N2O5 C 68.79, H 6.46, N 6.42; found C
68.67, H 6.62, N 6.35%.
;
1255, 1135, 732, and 666 cm21 1H NMR (CDCl3,
300 MHz) d 1.01 (3H, t, Jˆ7.4 Hz), 1.07 (3H, s), 1.14
(3H, s), 1.18±1.22 (1H, m), 1.45±1.62 (3H, m), 1.70±1.81
(2H, m), 1.70±1.82 (2H, m), 1.97±2.00 (2H, m), 2.27 (1H,
dd, Jˆ9.1 and 3.0 Hz), 2.34 (2H, t, Jˆ7.3 Hz), 2.73±2.77
(2H, m), 3.67 (3H, s), 3.68 (2H, brs), 6.46 (1H, s), 7.03 (1H,
s) and 7.22 (1H, brs); 13C NMR (CDCl3, 75.5 MHz) d 13.8,
19.2, 19.7, 20.1, 26.1, 27.6), 29.9, 32.1, 37.0, 37.9, 38.9,
45.1, 45.8, 51.6, 117.8, 123.0, 127.1, 135.1, 137.3, 138.2,
171.8 and 179.7; MS m/z 372 [M]1 (22%), 357 (21%), 297
(40%), 279 (100%) and 43 (30%). Anal. Calcd for
C22H32N2O3 C 70.94, H 8.66, N 7.52; found C 70.60, H
8.75, N 7.43%. HRMS: Calcd for C22H32N2O3 326.19943;
found 326.19931.
3.2.9. Methyl (4R,4aR,11bR)-2,3,4,4a,5,6,8,11b-octahydro-
4,9,11b-trimethyl-1H-phenanthro[2,3-d]imidazole-4-
carboxylate 4a. (a) Reduction. A mixture of the nitro-
acetamide 6a (73 mg, 0.19 mmol), Pd/C 10% (21 mg) and
ethanol (8 mL) was hydrogenated (H2, 50 psi) in a pressure
reactor at rt. After the reaction was complete (TLC), the
reaction mixture was ®ltered over Celite, washed with
dichloromethane and the solution evaporated to dryness.
The residue obtained (73 mg) was puri®ed by silica column
chromatography using dichloromethane±methanol (9:1) to
give the amine 8a (56 mg, 0.16 mmol, 84%) as an oil; IR
(®lm) nmax 3345, 2933, 1723, 1661, 1509, 1248, 1134 and
730 cm21; 1H NMR (CDCl3, 300 MHz) d 1.07 (3H, s), 1.14
(3H, s), 1.19±1.26 (1H, m), 1.41±1.61 (3H, m), 1.68±1.80
(2H, m), 1.93±2.01 (2H, m), 2.14 (3H, s), 2.26 (1H, dd,
Jˆ10.6 and 3.5 Hz), 2.72±2.77 (2H, m), 3.67 (3H, s), 3.68
(2H, brs), 6.45 (1 H), 7.00 (1H, s) and 7.37 (1H, brs); 13C
NMR (CDCl3, 75.5 MHz) d 19.7, 20.1, 23.5, 26.1, 27.6,
29.9, 32.0, 37.0, 37.9, 45.1, 45.8, 51.6, 117.7, 122.8, 123.3,
135.4, 138.0, 138.4, 169.0 and 179.7; MS m/z 344 [M]1
(43%), 329 (43%), 269 (100%) and 251 (47%). HRMS:
Calcd for C20H28N2O3 344.20996; found 344.21052.
(b) Cyclization. The amine 8b (50 mg, 0.125 mmol), xylene
(3 mL), and acetic acid (1 mL) were heated under re¯ux for
40 min. The solution was evaporated to dryness after cool-
ing the reaction mixture to rt. After puri®cation of the reac-
tion mixture by silica column chromatography using
dichloromethane±methanol (19.1), a white foam of the imi-
dazole 4b (30 mg, 0.085 mmol, 67%) was obtained; IR nmax
1
2940, 1726, 1462, 1250, 1194, 1135, and 731 cm21; H
NMR (CDCl3, 300 MHz) d 0.96 (3H, t, Jˆ7.3 Hz), 1.00
(3H, s), 1.22 (3H, s), 1.18±1.29 (1H, m), 1.51±1.63 (3H,
m), 1.72±1.76 (1H, m), 1.85 (2H, q, Jˆ7.3 Hz), 1.91±1.95
(2H, m), 1.99±2.09 (1H, m), 2.36 (1H, dd, Jˆ9.4 and
3.6 Hz), 2.88 (2H, t, Jˆ7.3 Hz), 2.94±2.99 (2H, m), 3.67
(3H, s), 7.18 (1H, s) and 7.46 (1H, s); 13C NMR (CDCl3,
75.5 MHz) d 13.8, 19.6, 20.4, 21.6, 25.1, 28.8, 30.9, 32.0,
32.6, 37.5, 38.7, 45.5, 46.0, 51.7, 111.7, 112.9, 131.1, 135.7,
137.2, 141.0, 155.1 and 179.6; MS m/z 354 [M]1 (17%), 339
(22%) and 279 (100%). HRMS: Calcd for C22H30N2O2
354.23071; found 354.23031.
(b) Cyclization. A mixture of the amine 8a (302 mg,
0.88 mmol), xylene (6 mL) and acetic acid (2 mL) was
heated under re¯ux for 15 min. The solution was evaporated
to dryness. After puri®cation of the residue by silica column
3.2.11. Methyl (4R,4aR,11bR)-4,11b-dimethyl-2,3,4,4a,
5,6,8,11b-octahydro-9-tri¯uoromethyl-1H-phenanthro-
[2,3-d]imidazole-4-carboxylate 4c. The nitroamide 6c
(111 mg, 0.26 mmol), K10 (211 mg), Pd/C 10% (29 mg)
and ethanol (7 mL) were heated under H2 (150 psi) at
1208C for 17 h. The imidazole 4c (95 mg, 0.25 mmol,
97%) was obtained as a white foam; IR nmax 2927, 1727,
1461, 1251, and 1139 cm21; 1H NMR (CDCl3, 300 MHz) d
0.99 (3H, s), 1.25 (3H, s), 1.25±1.32 (1H, m), 1.53±1.66
(3H, m), 1.76±1.78 (1H, m), 1.96±2.01 (2H, m), 2.11±2.16
(1H, m), 2.41 (1H, dd, Jˆ9.0 and 4.8 Hz), 3.00±3.02 (2H,
m), 3.70 (3H, s), 7.36 (1H, s) and 7.65 (1H, s); 13C NMR
(CDCl3, 75.5 MHz) d 19.4, 20.6, 23.5, 29.8, 30.0, 33.8,
37.7, 38.9, 45.9, 46.4, 51.6, 113.8, 114.7, 117.4 (t,
Jˆ271 Hz), 135.8, 137.8, 141.2 (q, Jˆ43.1 Hz), 143.5 and
179.6; MS m/z 380 [M]1 (10%), 365 (11%), 361 (3%), 333
(4%), and 305 (100%). HRMS: Calcd for C20H23N2O2F3
380.17114; found 380.17102.
chromatography
using
dichloromethane±methanol
(9.5:0.5), the imidazole 4a (221 mg, 0.68 mmol, 77%) was
obtained by recrystallization; mp 133±1358C (from
toluene); IR nmax 2938, 1727, 1463, 1248, 1194, 1135 and
730 cm21; 1H NMR (CDCl3, 300 MHz) d 1.00 (3H, s), 1.24
(3H, s), 1.26±1.30 (1H, m), 1.55±1.68 (3H, m), 1.71±1.79
(2H, m), 1.82±2.00 (1H, m), 2.03±2.12 (1H, m), 2.38 (1H,
dd, Jˆ9.4 and 3.0 Hz), 2.58 (3H, s), 2.94±2.98 (2H, m), 3.68
(3H, s), 7.17 (1H, s) and 7.45 (1H, s); 13C NMR (CDCl3,
75.5 MHz) d 14.8, 19.5, 20.5, 24.1, 29.6, 30.0, 33.6, 37.7,
38.7, 46.2, 51.5, 111.5, 113.1, 131.2, 136.5, 138.0, 140.8,
150.9 and 179.5; MS m/z 326 [M]1 (18%), 311 (27%), 251
(100%) and 84 (31%). Anal. Calcd for C20H26N2O2 C 73.59,
H 8.03, N 8.58; found C 73.29, H 8.06, N 7.97%. HRMS:
Calcd for C20H26N2O2 326.19943; found 326.19931.
3.2.10. Methyl (4R,4aR,11bR)-4,11b-dimethyl-2,3,4,4a,
5,6,8,11b-octahydro-9-propyl-1H-phenanthro[2,3-d]imi-
dazole-4-carboxylate 4b. (a) Reduction. By the procedure
3.2.12. Methyl (4R,4aR,11bR)-4,11b-dimethyl-2,3,4,4a,
5,6,8,11b-octahydro-1H-phenanthro[2,3-d]imidazole-4-

1798
T. Fonseca et al. / Tetrahedron 57 (2001) 1793±1799
carboxylate 4dA mixture the formamide 6d (70 mg,
0.194 mmol), K10 (175 mg), Pd/C 10% (20 mg) and ethanol
(10 mL) was hydrogenated (H2, 100 psi) at 1208C overnight
(16.5 h) with vigorous stirring. After cooling to rt, the reac-
tion mixture was ®ltered over Celite and washed with
dichloromethane, that after evaporation to dryness gave a
white foam of the imidazole 4d (58 mg, 0.186 mmol, 96%);
IR nmax 2943, 1723, 1583, 1462, 1249, 1194, 1135 and
tion was followed by TLC and after it was complete (1 h)
the claycop was ®ltered off and the ®lter cake was washed
with dichloromethane. The organic phases were washed
with water followed by sodium hydrogencarbonate and
dried over anhydrous sodium sulfate. After evaporation of
the solvents the solid residue (477 mg) was puri®ed by silica
column chromatography using dichloromethane±ethyl ace-
tate (9:1) as eluent. Yellow crystals of 2-nitroacetanilide
(355 mg, 1.97 mmol, 90%) were obtained, mp 91±928C
(lit.10 91±928C).
1
731 cm21; H NMR (CDCl3, 300 MHz) d 0.99 (3H, s),
1.26 (3H, s), 1.26±1.32 (1H, m), 1.50±1.68 (3H, m),
1.68±1.78 (1H, m), 1.91±1.99 (2H, m), 2.01±2.14 (1H,
m), 2.39 (1H, dd, Jˆ9.1 and 4.0 Hz), 2.99±3.03 (2H, m),
3.69 (3H, s), 7.29 (1H, s), 7.58 (1H, s) and 8.00 (1H, s, 9-H);
13C NMR (CDCl3, 75.5 MHz) d 19.6, 20.5, 24.7, 29.2, 30.3,
33.0, 37.6, 38.8, 45.8, 46.0, 51.7, 112.6, 113.9, 132.0, 135.4,
137.1, 140.7, 141.7 and 179.7; MS m/z 312 [M]1 (12%), 297
(20%) and 237 (100%). HRMS: Calcd for C19H24N2O2
312.18378; found 312.18365.
3.2.15. 2-Nitrobutyranilide 9b. A solution of aniline
(0.2 mL, 2.19 mmol) in carbon tetrachloride (3 mL) was
added with vigorous stirring to butyric anhydride (0.5 mL,
3 mmol) in carbon tetrachloride (4 mL) in an ice-salt bath.
After the aniline had been consumed (TLC), `claycop'
(1.55 g, 6.72 mmol), followed by acetic anhydride
(3.5 mL, 36.6 mmol) were then added, with vigorous stir-
ring. The ice bath was removed and the reaction continued
at rt. After 2 h, the reaction was worked-up as for 9a to give
a solid residue (509 mg) that was puri®ed by silica column
chromatography using dichloromethane. Yellow crystals of
2-nitrobutyranilide 9b (373 mg, 1.79 mmol, 82%) were
obtained, mp 49±49.58C (lit.11 50±518C).
3.2.13. Methyl (4R,4aR,11bR)-4,11b-dimethyl-2,3,4,4a,
5,6,8,11b-octahydro-9-phenyl-1H-phenanthro[2,3-d]imi-
dazole-4-carboxylate 4e. (a) Reduction. The nitroamide 6e
(150 mg, 0.38 mmol) and Pd/C 10% (36 mg) in ethanol
(10 mL) was hydrogenated under H2 (60 psi) at rt for 2 h.
Column chromatography using dichloromethane±methanol
(24:1) gave the amine 8c as a white foam (131 mg,
0.32 mmol, 85%); IR nmax 3343, 2943, 1723, 1649, 1516,
3.2.16. 2-Nitrotri¯uoroacetanilide 9c. By the procedure
described for the amide 9b, TFAA (0.35 mL, 2.5 mmol),
aniline (0.2 mL, 2.19 mmol), carbon tetrachloride (7 mL),
`claycop' (1.55 g, 6.72 mmol) and acetic anhydride
(3.5 mL, 36.6 mmol) gave (2 h) a solid product (453 mg).
By silica column chromatography with dichloromethane-
light petroleum (3:2) as eluent, 2-nitrotri¯uoroacetanilide
9c was eluted ®rst to give yellow crystals (205 mg,
0.86 mmol, 40%), mp 86±878C (lit.12 86±878C).
1
1256, 1136, and 731 cm21; H NMR (CDCl3, 300 MHz) d
1.08 (3H, s), 1.16 (3H,s), 1.20±1.26 (1H, m), 1.43±1.63
(3H, m), 1.69±1.82 (2H, m), 1.96±2.03 (2H, m), 2.28
(1H, dd, Jˆ10.4 and 3.0 Hz), 2.74±2.80 (2H, m), 3.67
(3H, s), 3.73 (2H, brs), 6.50 (1H, s), 7.20 (1H, s), 7.46
(1H, brs), 7.43±7.56 (3H, m) and 7.81±7.91 (2H, m); 13C
NMR (CDCl3, 75.5 MHz) d 19.7, 20.1, 26.0, 27.7, 29.9,
32.2, 37.0, 37.9, 45.1, 45.8, 51.6, 118.0, 122.9, 123.1,
127.4, 128.8, 131.8, 134.4, 135.2, 138.1, 138.2, 165.9 and
179.7; MS m/z 406 [M]1 (10%), 373 (19%), 313 (100%),
105 (61%) and 77 (27%). HRMS: Calcd for C25H30N2O3
406.22562; found 406.22538.
Further elution with dichloromethane gave 4-nitrotri¯uoro-
acetanilide (267 mg, 1.14 mmol, 52%) as a yellow solid, mp
150±1528C (lit.13 151±1538C).
3.2.17. 2-Nitroformanilide 9d. Acetic-formic anhydride
was prepared in situ from formic acid (0.17 mL,
4.35 mmol) and acetic anhydride (0.42 mL, 4.38 mmol).
Carbon tetrachloride (5 mL) was added followed by drop-
wise addition of aniline (0.4 mL, 4.35 mmol) in carbon
tetrachloride (5 mL) at 2108C. After the aniline had reacted
(TLC) `claycop' (2.33 g, 10.13 mmol) then acetic anhydride
(6.5 mL, 67.9 mmol) were added to the reaction mixture.
After 2.5 h the `claycop' was ®ltered off. After workup,
the solid residue (883 mg) was puri®ed by silica column
chromatography using light petroleum±ethyl acetate (3:2).
Pale yellow crystals of 2-nitroformanilide 9d (498 mg,
3.0 mmol, 69%) were obtained, mp 118.5±119.58C (lit.14
122±1238C).
(b) Cyclization. The amine 8c (87 mg, 0.21 mmol), xylene
(3 mL) and acetic acid (0.5 mL) were heated under re¯ux
and under nitrogen for 1 h. The solution was evaporated to
dryness after cooling the reaction mixture to rt. After puri-
®cation by silica column chromatography using dichloro-
methane±methanol (24:1), yielded the imidazole 4e (72 mg,
0.18 mmol, 88%) as a white foam; IR nmax 2947, 1726,
1463, 1194, 1136, and 732 cm21 1H NMR (CDCl3,
;
300 MHz) d 0.98 (3H, s), 1.19 (3H, s), 1.21±1.26 (1H,
m), 1.45±1.62 (3H, m), 1.62±1.75 (1H, m), 1.84±1.99
(2H, m), 2.04±2.14 (1H, m), 2.36 (1H, dd, Jˆ9.0 and
4.0 Hz), 2.86±3.00 (2H, m), 3.68 (3H, s), 7.19 (1H, s),
7.33±7.37 (3H, m), 7.49 (1H, s) and 8.10±8.13 (2H, m);
13C NMR (CDCl3, 75.5 MHz) d 19.5, 20.5, 24.6, 29.2, 30.2,
33.1, 37.5, 38.7, 45.8, 46.0, 51.7, 112.5, 113.5, 126.9, 129.0,
129.9, 130.2, 131.9, 137.0, 138.9, 141.5, 152.3 and 179.8; MS
m/z 388 [M]1 (25%), 373 (21%) and 313 (100%). HRMS:
Calcd for C25H28N2O2 388.21506; found 388.21534.
3.2.18. 2-Nitrobenzanilide 9e. Benzoic anhydride (509 mg,
2.25 mmol), aniline (0.2 mL, 2.19 mmol) and carbon tetra-
chloride (10 mL), `claycop' (2.09 g, 9.1 mmol) and acetic
anhydride (5.66 mL, 59.18 mmol) reacted for 4 h as
described for the preparation of amide 9b. The solid
obtained was puri®ed by silica column chromatography
using dichloromethane±light petroleum (3:2) to give
2-nitrobenzanilide 9e (317 mg, 1.31 mmol, 60%), mp
92.4±93.38C (lit.15 94±958C).
3.2.14. 2-Nitroacetanilide 9a. Aniline (0.2 mL, 2.19 mmol)
was added with vigorous stirring to a mixture of claycop
(1.06 g, 4.6 mmol), acetic anhydride (3.3 mL, 34.4 mmol)
and carbon tetrachloride (6.6 mL) in an ice-bath. The reac-

T. Fonseca et al. / Tetrahedron 57 (2001) 1793±1799
1799
3.3. Two step conversion of amides 9 into benzimidazoles
PhD grant (BD 11539/97) (to T. F.) and A. I. Rodrigues for
2-D NMR spectra.
3.3.1. General procedure. The appropriate amide in
ethanol was hydrogenated over 10% Pd/C at rt under hydro-
gen (50 psi). The amine obtained was isolated and cyclized
by heating under re¯ux in xylene±acetic acid (13:1) for
0.5±2 h.
References
1. Buchbauer, G.; Kolbe, R. Sci. Pharm. 1985, 53, 173±202. San
Feliciano, A.; Gordazila, M.; Salinero, M. A.; Corral, J. M. M.
Planta Med. 1993, 59, 485±490.
The following compounds were prepared in this way:
2. Ohta, M.; Ohmori, L. Chem. Pharm. Bull. 1957, 5, 91±95.
3. Feio, S. S.; Gigante, B.; Roseiro, J. C.; Marcelo-Curto, M. J.
J. Microbiol. Methods 1999, 35, 201±206 (and references
therein).
2-Aminoacetanilide 10a (91% from 9a), mp 124±1268C
(lit.10 130±1318C).
Ã
4. Gigante, B.; Prazeres, A. O.; Marcelo-Curto, M. J. J. Org.
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2-Methylbenzimidazole 11a (97% from 10a), mp 170±
1728C (lit.16 175±1768C).
5. Gigante, B.; Sequeira, M. F.; Guerreiro, A. M.; Santos, L.;
Santos, M. A.; Marcelo-Curto, M. J. In Recent Discoveries
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M. I., Sheikani, M. S., Eds.; Elite: Karachi, Pakistan, 1996;
pp 37±43.
2-Aminobutyranilide 10b (81% from 9b), mp 123±1248C
(lit.17 1318C).
2-Propylbenzimidazole 11b (81% from 10b) mp 152±
1538C (lit.18 156±157.58C).
6. Grimmett, M. R. Imidazole and Benzimidazole Synthesis;
Academic: London, 1997.
7. Halbrook, N. J.; Lawrence, R. V. J. Org. Chem. 1966, 31,
4246±4247.
2-Aminobenzanilide 10c (95% from 9e), mp 145±1478C
(lit.19 148±1518C).
8. Fujii, R.; Arimoto, K.; Zinkel, D. F. J. Am. Oil Chem. Soc.
1987, 64, 1144±1149.
Â
9. Cornelis, A.; Laslo, P. Synthesis 1985, 909±918.
2-Phenylbenzimidazole 11e (54% after column chromato-
graphy), mp 2958C (lit.20 2958C).
10. Gribble, G. W.; Bousquet, F. P. Tetrahedron 1971, 27, 3785±
3794.
3.4. One step conversion of amides 9 into benzimidazoles
11. Gertler, S. I.; Yerrington, A. P., US Dept. Agr., Agr. Res.
Service, Entomol. Res. Branch, ARS-3-31 1956 (Chem.
Abstr. 1956, 50, 17297).
The following benzimidazoles were prepared directly from
the appropriate amides 9.
12. Morgan, K. J.; Turner, A. M. Tetrahedron 1969, 25, 915±927.
13. Staab, H. A.; Walther, G. Chem. Ber. 1962, 95, 2070±2072.
14. Sekiya, M.; Takayama, S. Chem. Pharm. Bull. 1970, 18,
2146±2150.
3.4.1. 2-Tri¯uoromethylbenzimidazole 11c. 2-Nitro-
tri¯uoroacetanilide 9c (102 mg, 0.44 mmol), K10
(306 mg) and Pd/C 10% (49 mg) were heated in ethanol
(10 mL) under H2 (130 psi) at 1208C for 18 h. 2-Tri¯uoro-
methylbenzimidazole 11c (71 mg, 0.38 mmol, 88%) was
obtained as a white precipitate after evaporation of the
solvent; mp 205±2088C (lit.12 209±2108C).
15. Cadogan, J. I. G.; Marshall, R.; Smith, D. M.; Todd, M. J.
J. Chem. Soc. C 1970, 2441±2443.
16. Howe, R.; Johnson, D. J. Chem. Soc., Perkin Trans. 1 1972,
977±981.
17. Morgan, K. J.; Turner, A. M. Tetrahedron 1966, 22, 1175±
1181.
3.4.2. Benzimidazole 11d. 2-Nitroformanilide 9d (45 mg,
0.297 mmol), K10 (266 mg), and Pd/C 10% (30 mg) were
heated in ethanol (10 mL) under H2 (150 psi), at 1208C for
16 h. After evaporation of the solvent, 11d (24 mg,
0.21 mmol, 70%) was obtained as a white precipitate; mp
170±1718C (lit.21 173±1748C).
18. Hay, J. V.; Portlock, D. E.; Wolfe, J. F. J. Org. Chem. 1973,
38, 4379±4382.
19. Ruggli, P.; Rohner, J. Helv. Chim. Acta 1942, 25, 1533±1542.
20. Thomas, P. R.; Tyler, G. J. J. Chem. Soc. 1957, 2197±2201.
Ï
21. Stanovnik, B.; Tisler, M. Synthesis 1974, 120±122.
Acknowledgements
Ã
We thank FundacËaÄo para Ciencia e Tecnologia (FCT) for a