Catalyst/ligand-free synthesis of benzimidazoles and quinazolinones from amidines via intramolecular transamination reaction

Article abstract of DOI:10.1016/j.tetlet.2010.02.019

An efficient catalyst/ligand-free synthesis of benzimidazoles and quinazolinones from amidines in quantitative yields has been described.

Full text of DOI:10.1016/j.tetlet.2010.02.019

Tetrahedron Letters 51 (2010) 1887–1890
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Tetrahedron Letters
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Catalyst/ligand-free synthesis of benzimidazoles and quinazolinones
from amidines via intramolecular transamination reaction
*
Sahaj Gupta, Piyush K. Agarwal, Bijoy Kundu
Medicinal Chemistry Division, Central Drug Research Institute, CSIR, Lucknow 226 001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient catalyst/ligand-free synthesis of benzimidazoles and quinazolinones from amidines in quan-
titative yields has been described.
Received 14 December 2009
Revised 29 January 2010
Accepted 5 February 2010
Available online 8 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
N-Heterocycles have always remained a major source for thera-
peutic drugs with benzimidazoles1 and quinazolinones2 being the
ones receiving significant attention. The synthesis of these heterocy-
clic structures is pivotal for the success of implementation of organic
synthesis in the drug discovery process. Although a number of meth-
ods dealing with the synthesis of these heterocycles have appeared,
new routes from new set of monomers remain the subject of contin-
uous investigation.
Our synthesis (Scheme 1) commenced with the N-arylation of
amidine 1a by treating it with 2-fluoronitrobenzene 2a resulting
in a key intermediate N-(2-nitrophenyl)benzene-carboximidamide
3a via nucleophilic substitution reaction in 30 min under micro-
wave conditions. Under conventional heating conditions the yield
of N-(2-nitrophenyl)benzenecarboximidamide 3a was poor and re-
quired longer reaction time. In order to increase the variation in 3,
the strategy was then successfully applied to the synthesis of 14 N-
arylated substrates 3b–o by treating several aliphatic/aromatic
amidines with 2-fluoronitrobenzene derivatives. In general the
compounds 3 were obtained in >90% isolated yields and were char-
acterized using NMR and ESMS.8 In the next step, the nitro group of
N-(2-nitrophenyl)benzenecarboximidamide 3a was initially sub-
jected to reduction via hydrogenation using 10% Pd/C in ethanol
and progress of the reaction was monitored by both TLC and HPLC.
The conversion of the nitro derivative 3a was found to be complete
within 15 min and the product even after 24 h of stirring at rt
In recent years syntheses of benzimidazoles and quinazolinones
have been affected using amidines as a building block albeit in the
presence of catalysts and/or ligands as additive. Brain and Brunton3
described the synthesis of benzimidazoles using (o-bromophenyl)
amidine precursor but the strategy suffers from the disadvantage
that the product gets contaminated with the ligand and an extra
step is involved in the purification. Brasche and Buchwald4 used
N-phenylbenzamidine for the copper-catalyzed synthesis of benz-
imidazoles, however, in the case of 2-alkylbenzimidazole it was
limited to amidines bearing a bulky tert-butyl group. Hu and co-
workers5 synthesized benzimidazoles via cascade reactions of o-
haloacetoanilide derivatives with amidine hydrochlorides using
10 mol % CuBr as catalyst. Deng et al.6 reported a facile synthesis
of benzimidazoles by treating dihalobenzenes with guanidines or
amidines in the presence of CuI and L5 (N,N-dimethylethylenedi-
amine). Similarly, for the synthesis of quinazolinones, Fu and co-
workers7 treated amidines with 2-bromobenzoic acid in the pres-
ence of copper followed by intramolecular cyclization. Thus, all
the above strategies involved the use of either a catalyst and/or a
ligand for the C–N bond formation thereby leading to the synthesis
of benzimidazoles and quinazolinones. In this Letter, we report a
simple and efficient method for the synthesis of benzimidazoles
and quinazolinones from amidines without involving the use of
catalysts and/or ligands for the C–N bond formation.
R
NH
NH
NH
O2N
F
R1
R2
(i)
R
R2
R1
NH2
NO2
2a R1 = H, R2 = H
2b R1 = H, R2 = CH3
2c R1 = CF3, R2 = H
1a R = Ph,
3a-o
1b R = 4-OCH3-Ph
1c R = 4-CH3-Ph
1d R = 3-CH3-Ph
1e R = CH3
(ii)
R
NH
R2
R1
R2
R1
NH
NH2
N
R
N
H
5a-o
4
* Corresponding author. Tel.: +91 522 2612411x18; fax: +91 522 2623405.
E-mail addresses: bijoy_kundu@yahoo.com, b_kundu@cdri.res.in (B. Kundu).
CDRI Communication No. 7923.
Scheme 1. Reagents and conditions: (i) K2CO3, DMSO, 110 °C,
Pd–C, HCOONH4, CH3COOH, 80 °C, 1 h.
lW, 30 min; (ii) 10%
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.019

1888
S. Gupta et al. / Tetrahedron Letters 51 (2010) 1887–1890
Table 2
NH
NH
NH
NH2
NO2
Synthesis of benzimidazoles 5a–o
H
Entry
Substrate
R
R1
R2
Product
Yield (%)
NH
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3°
C6H5–
C6H5–
C6H5–
H
H
CF3
H
H
CF3
H
H
CF3
H
H
H
CH3
H
H
CH3
H
H
CH3
H
H
CH3
H
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
96
97
91
95
93
94
97
95
90
92
93
97
96
93
91
4
3a
4-(OCH3)–C6H4–
4-(OCH3)–C6H4–
4-(OCH3)–C6H4–
4-(CH3)–C6H4–
4-(CH3)–C6H4–
4-(CH3)–C6H4–
3-(CH3)–C6H4–
3-(CH3)–C6H4–
3-(CH3)–C6H4–
CH3
H
N
H
NH3
H
N
H2N
HN
5a
N
H
N
H
CF3
H
H
H
CH3
H
CH3
CH3
Figure 1. Proposed mechanism for the synthesis of 5a.
CF3
remained a mixture of two components. The HPLC exhibited a ma-
jor peak in 51% yield (area under the curve) and the second compo-
nent in 43% yield. The two components were separated by column
chromatography and characterized by ESMS and NMR. One of the
components with higher Rf on TLC was obtained in 42% isolated
yield (mass of 194.2 Da) and was found to be benzimidazole deriv-
ative 5a. The second component with the lower Rf and mass of
211.2 Da corresponded to the mass of amino component 4 but
could not be characterized by the NMR as it had tendency to un-
dergo slow cyclization to 5a. The formation of the product 5a
may have occurred from an intramolecular cyclization via sequen-
tial C–N bond formation and dissociation resulting in benzimid-
azole. A plausible mechanism for the intramolecular cyclization
following reduction of the aryl nitro group in 3a has been depicted
in Figure 1. The reaction commences with the nucleophilic attack
of the aryl amino function 4 on to the electrophilic carbon of the
amidine followed by an intramolecular transamination (addition–
elimination of NH2) reaction. The aromatization then occurred
with the elimination of ammonia to yield benzimidazole.
nation conditions involving 10% Pd/C in AcOH using ammonium
formate as a hydrogen donor at 80 °C for 1 h.9 The resulting crude
product obtained after work-up exhibited >98% purity on HPLC and
was therefore simply triturated with 5:1 hexane/ether to furnish
benzimidazole 5a in 96% isolated yield. In general, it appears that
although the amine component was formed within 15 min under
all reductive conditions, the transamination leading to the forma-
tion of 5a required elevated temperatures and acidic conditions.
To further substantiate this, in one of the experiments, the sub-
strate 3a was subjected to catalytic reduction by passing hydrogen
in the presence of 10% Pd/C in EtOH–AcOH mixture (1:1). After
15 min Pd/C was removed by filtration and the filtrate was heated
at 80 °C for 1 h which in turn furnished 5a in quantitative yield.
Once we optimized the reaction condition for the conversion of
3a–5a, we next examined the scope and limitation of our strategy
by synthesizing 14 benzimidazole derivatives 5b–o using aromatic
and aliphatic amidine-derived substrates 3b–o and in all the cases
the product was isolated in 90–97% yields after crystallization (Ta-
ble 2). This is in contrast to catalyst- and/or ligand-driven reactions
reported in the literature from amidines wherein yields of benz-
imidazole ranged between 60% and 80% and involved purification
using column chromatography as an additional step. Of the fifteen
benzimidazole derivatives synthesized, physico-chemical parame-
ters of 12 compounds (5a–h, 5j, and 5m–o) matched with the ones
reported in the literature.10
After establishing the methodology for benzimidazoles, we next
focused our attention on the synthesis of yet another important
six-membered N-heterocycle quinazolinones. The substrate N-[imi-
no(phenyl)methyl]-2-nitrobenzamide 7a required for the synthesis
of quinazolinone was prepared (Scheme 2) by the coupling of ben-
zenecarboximidamide 1a and 2-nitrobenzoic acid 6a. The strategy
was then successfully used to synthesize 14 substrates 7b–o by cou-
pling several aliphatic/aromatic amidines with 2-nitrobenzoic acid
derivatives. The resulting N-acylated compounds 7 after purification
via either crystallization or column chromatography were charac-
terized using NMR and ESMS.11 It is worth mentioning that acylation
Thus our method, unlike the reported strategies2–6 did not in-
volve the use of either catalysts such as copper/Pd(PPh3)4 or li-
gands for the C–N bond formation. The Pd/C used on our
methodology was involved in the functional group transformation
from nitro to amine which in turn triggered the intramolecular
transamination reaction. This led us to optimize the reaction con-
ditions for the quantitative conversion of 3a into 5a by carrying out
the reduction of the nitro group under other reducing conditions
and the results have been summarized in Table 1. Reduction of
3a in the presence of 10% Pd/C in ethanol at rt for 24 h furnished
benzimidazole 5a in 42% yield, in contrast, when the same reaction
mixture was heated, 5a could be isolated in 65% yield. Addition of
acid to the reaction mixture followed by heating at 80 °C for 1 h
improved the yield to 85% (entry 3). Similarly, reduction with
SnCl2Á2H2O at 80 °C in ethanol and with Fe/AcOH at 80 °C furnished
5a in 72% and 77% yield, respectively within 1 h. However, the
complete conversion of 3a into 5a was observed when reduction
of the nitro group was carried out under catalytic transfer hydroge-
Table 1
Optimization of reaction conditions for the conversion of 3a into 5a
Entry
Reaction conditions
Temp (°C)
Time (h)
Yield of 5a (%)
1
2
3
4
5
6
7
10% Pd/C, H2, in ethanol
10% Pd/C, H2, in ethanol
10% Pd/C, H2, in 20% MeOH/AcOH
Fe/AcOH
rt
24
1
1
1
1
42
65
85
77
72
60
96
80 °C
80 °C
80 °C
80 °C
rt
SnCl2Á2H2O in ethanol
10% Pd/C in AcOH, HCOONH4
10% Pd/C in AcOH, HCOONH4
12
1
80 °C

S. Gupta et al. / Tetrahedron Letters 51 (2010) 1887–1890
1889
Acknowledgment
R3
R4
O
NH
O2N
HO
NH
R4
R3
R
(i)
N
H
R
S.G. and P.K.A. are thankful to CSIR, New Delhi, India, for
fellowships.
NH2
NO2
7a-o
O
1a R = Ph,
6a R3 = H, R4 = H
References and notes
6b R3 = H, R4 = CH3
6c R3= OCH3, R4 = H
1b R = 4-OMe-Ph
1c R = 4-Me-Ph
1d R = 3-Me-Ph
1e R = CH3
(ii)
1. (a) Grimmett, M. R.. In Comprehensive Heterocyclic Chemistry; Katrizky, A. R.,
Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; 3, pp 77–220; (b)
Kim, J. S.; Gatto, B.; Yu, C.; Liu, L. F.; Lavoie, E. J. J. Med. Chem. 1996, 39, 992;
Greenhill, J. V.; Lue, L.. In Progress in Medicinal Chemistry; Ellis, G. P., Luscombe,
D. K., Eds.; Elsevier: New York, 1993; Vol. 3, (c) Erhardt, P. W. J. Med. Chem.
1987, 30, 231; (d) Tomczuk, B. E.; Taylor, C. R., Jr.; Moses, L. M.; Sutherland, D.
B.; Lo, Y. S.; Johnson, D. N.; Kinnier, W. B.; Kilpatrick, B. F. J. Med. Chem. 1991, 34,
2993; (e) LaPlante, S. R.; Jakalian, A.; Aubry, N.; Bousquet, Y.; Ferland, J.-M.;
Gillard, J.; Lefebvre, S.; Poirier, M.; Tsantrizos, Y. S.; Beaulieu, P. L. Angew. Chem.,
Int. Ed. 2004, 43, 4306; (f) Preston, P. N. Chem. Rev. 1974, 74, 279; (g) Spasov, A.
A.; Yozhitsa, I. N.; Bugaeva, L. I.; Anisimova, V. A. Pharm. Chem. J. 1999, 33, 232;
(h) Touzeau, F.; Arrault, A.; Guillaumet, G.; Scalbert, E.; Pfeiffer, B.; Rettori, M.-
C.; Renard, P.; Merour, J.-Y. J. Med. Chem. 2003, 46, 1962.
O
N
R4
R3
NH
R
8a-o
Scheme 2. Reagents and conditions: (i) DCC, HOBT, DMF, rt, 12 h; (ii) 10% Pd–C,
HCOONH4, CH3COOH, 80 °C, 1 h.
2. (a) Mhaske, S. B.; Argade, N. P. Tetrahedron 2006, 62, 9787; (b) Witt, A.;
Bergman, J. Curr. Org. Chem. 2003, 7, 659; (c) Connolly, D. J.; Cusack, D.;
O_Sullivan, T. P.; Guiry, P. J. Tetrahedron 2005, 61, 10153; (d) Ma, Z.; Hano, Y.;
Nomura, T. Heterocycles 2005, 65, 2203.
Table 3
Synthesis of quinazolinones 8a–o
3. (a) Brain, C. T.; Brunton, S. A. Tetrahedron Lett. 2002, 43, 1893; (b) Brain, C. T.;
Steer, J. T. J. Org. Chem. 2008, 71, 6814.
Entry
Substrate
R
R3
R4
Product
Yield (%)
4. Brasche, G.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 1932.
5. Yang, D.; Fu, H.; Hu, L.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2008, 73, 7841.
6. Deng, X.; McAllister, H.; Mani, N. S. J. Org. Chem. 2009, 74, 5742.
7. Liu, X.; Fu, H.; Jiang, Y.; Zhao, Y. Angew. Chem., Int. Ed. 2009, 48, 348.
8. The mixture of benzenecarboximidamide (0.50 g, 4.11 mmol), 1-fluoro-2-
nitrobenzene (0.57 g, 4.11 mmol), and potassium carbonate (0.62 g,
4.52 mmol) in DMSO (5 ml) was taken in a microwave vial. The solution was
heated at 110 °C for 30 min in microwave (Biotage). The reaction mixture was
cooled to room temperature, water was added, and the compound was
extracted with ethyl acetate (15 mL Â 3). The organic layer was washed with
brine, dried over Na2SO4, and concentrated in vacuo to get the crude product
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
C6H5–
C6H5–
C6H5–
H
H
OCH3
H
H
OCH3
H
H
OCH3
H
H
H
CH3
H
H
CH3
H
H
CH3
H
H
CH3
H
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
96
91
95
97
92
96
91
95
93
94
91
94
93
95
96
4-(OCH3)–C6H4–
4-(OCH3)–C6H4–
4-(OCH3)–C6H4–
4-(CH3)–C6H4–
4-(CH3)–C6H4–
4-(CH3)–C6H4–
3-(CH3)–C6H4–
3-(CH3)–C6H4–
3-(CH3)–C6H4–
CH3
which was triturated with 9:1 hexane–diethyl ether to afford
compound which was used without further purification.
a yellow
OCH3
H
H
4-Methoxy-N-(5-methyl-2-nitrophenyl)benzene carboximidamide (3e): Yield =
0.87 g (92%), yellow oil, Rf = 0.48 (1:1 EtOAc–hexane), IR (KBr) mmax 2920,
H
CH3
H
CH3
CH3
1639, 1388, 1260 cmÀ1 1H NMR (300 MHz, CDCl3) d = 7.96–7.91 (1H, m, ArH),
;
OCH3
7.78 (2H, s, ArH), 6.98–6.93 (4H, m, ArH), 3.88 (3H, s, OCH3), 2.41 (3H, s, CH3);
13C NMR (50 MHz, CDCl3) d = 161.9, 145.7, 139.4, 129.8, 128.7, 127.6, 125.7,
124.8, 123.7, 114.3, 114.0, 55.5, 21.7; mass (ES+) m/z 286.1 (M++1); Anal. Calcd
for C15H15N3O3: C, 63.15; H, 5.30; N, 14.73. Found: C, 63.11; H, 5.28; N, 14.76.
9. To a stirred solution of N-(2-nitro-phenyl)-benzamidine (0.25 g, 1.04 mmol) in
acetic acid (2 ml) under nitrogen atmosphere were added ammonium formate
(0.40 g, 5.18 mmol) and palladium on carbon 10% wet (25 mg) at room
temperature. The reaction mixture was heated at 80 °C for 1 h. It was filtered
through Celite bed and washed with ethyl acetate. The filtrate was neutralized
with satd sodium bicarbonate. The compound was extracted with ethyl acetate
(15 mL Â 3). The organic layer was washed with brine, dried over Na2SO4, and
concentrated in vacuo. The crude product was triturated with 5:1 hexane–
diethyl ether to afford pure compound as white solid.
with aryl amidines (yield >90%) was more favored than that with ali-
phatic amidines (yield 51–53%). Next, for the transamination reac-
tion, the nitro group in the substrate 7a was subjected to reduction
with 10% Pd/C in AcOH using ammonium formate as a hydrogen do-
nor at 80 °C for 1 h. The resulting crude product obtained after work-
up was triturated with diethyl ether to furnish 2-phenylquinazolin-
4(3H)-one 8a12 in 96% isolated yield. Of the 15 quinazolinone deriv-
atives synthesized, physico-chemical parameters of 11 compounds
(8a–e, 8g–h, 8j, and 8m–o) matched with the ones reported in the
literature.7,13
The scope and limitation of our strategy were established by
synthesizing 14 compounds based on quinazolinone 8b–o (Table
3) using a variety of aromatic and aliphatic amidine-derived sub-
strates 7b–o and in all the cases the product was obtained in 91–
96% isolated yield after crystallization. In contrast, variable yields
of 40–87% were reported for quinazolinones from amidines in
the literature under copper-catalyzed conditions.7
In summary, we have developed a mild and efficient method
for the synthesis of highly substituted benzimidazole and qui-
nazolinone derivatives under catalyst and ligand-free conditions.
In general the strategy involves N-arylation and N-benzoylation
of amidines with o-nitro arenes followed by reduction of the ni-
tro group and intramolecular transamination reaction. The work-
up procedure was simple and isolation of the product without
column chromatography proved to be an added advantage for
the synthesis of benzimidazole and quinazolinone motifs. This
procedure will be a value addition for the synthesis of benzimid-
azole and quinazolinone derivatives of academic and industrial
importance.
2-Phenyl-1H-benzimidazole (5a): Yield = 0.19 g (96%), white solid, mp >250 °C
[lit.4 286–289], Rf = 0.48 (2:3 EtOAc–hexane), IR (KBr) mmax 3399, 1653, 1408,
1112 cmÀ1 1H NMR (300 MHz, DMSO-d6) d = 8.19–8.16 (2H, m, ArH), 7.61–
;
7.47 (5H, m, ArH), 7.23–7.18 (2H, m, ArH); 13C NMR (50 MHz, DMSO-d6)
d = 151.2, 130.1, 129.9, 128.9, 126.5, 122.1; mass (ES+) m/z 195.3 (M++1); Anal.
Calcd for C13H10N2: C, 80.39; H, 5.19; N, 14.42. Found: C, 80.43; H, 5.16; N,
14.41.
2-(4-Methylphenyl)-5-(trifluoromethyl)-1H-benzimidazole (5i): Yield = 0.19 g
(90%), white solid, mp 192–194 °C, Rf = 0.54 (2:3 EtOAc–hexane), IR (KBr)
m
max 3119, 1620, 1431, 1122 cmÀ1 1H NMR (300 MHz, DMSO-d6) d = 13.28 (1H,
;
s, NH), 8.13 (2H, d, J = 8.2 Hz, ArH), 7.96 (1H, s, ArH), 7.79 (1H, d, J = 8.4 Hz,
ArH), 7.56–7.54 (1H, m, ArH), 7.43 (2H, d, J = 8.0 Hz, ArH), 2.43 (3H, s, CH3);13
C
NMR (75 MHz, DMSO-d6) d = 154.1, 140.4, 129.6, 126.8, 122.8(d, J = 33.7 Hz),
122.4, 118.7, 20.9; mass (ES+) m/z 277.3 (M++1); Anal. Calcd for C15H11F3N2: C,
65.21; H, 4.01; N, 10.14. Found: C, 65.18; H, 4.00; N, 10.17.
10. (a) Lin, S.; Yang, L. Tetrahedron Lett. 2005, 46, 4315; (b) Lewis, J. C.; Wu, J. Y.;
Bergman, R. G.; Ellman, J. A. Angew. Chem., Int. Ed. 2006, 45, 1589; (c) Ji, Y.; Bur,
D.; Haesler, W.; Schmitt, V. R.; Dorn, A.; Bailly, C.; Waring, M. J.; Hochstrasser,
R.; Leupin, W. Bioorg. Med. Chem. 2001, 9, 2905; (d) Savall, B. M.; Fontimayor, J.
R. Tetrahedron Lett. 2008, 47, 6667; (e) Sharghi, H.; Beyzavi, M. H.;
Doroodmand, M. M. Eur. J. Org. Chem. 2008, 24, 4126; (f) Bougrin, K.;
Soufiaoui, M. Tetrahedron Lett. 1995, 36, 3683; (g) VanVliet, D. S.; Gillespie,
P.; Scicinski, J. J. Tetrahedron Lett. 2005, 46, 6741.
11. To a stirred solution of 2-nitrobenzoic acid (1.0 g, 6.66 mmol) in DMF (10 ml)
at 0 °C were added DCC (1.51 g, 7.33 mmol) and HOBT (0.99 g, 7.33 mmol) .The
reaction mixture was stirred at 0 °C for 1 h to which 4-methoxy-benzamidine
(1.22 g, 7.33 mmol) was added and allowed to stir at room temperature for
12 h. The reaction mixture was filtered through Celite bed and washed with
ethyl acetate. The filtrate was washed with brine, dried over Na2SO4, and

1890
S. Gupta et al. / Tetrahedron Letters 51 (2010) 1887–1890
concentrated to get the crude product, which was triturated with hexane and
used without any purification.
brine, dried over Na2SO4, and concentrated in vacuo. The crude product was
triturated with diethyl ether to afford pure compound as white solid.
2-(4-Methoxyphenyl)-6-methylquinazolin-4(3H)-one (8e): Yield = 0.2 g (92%),
white solid, mp >250 °C [lit.13d 258–259] Rf = 0.57 (2:5 EtOAc–hexane), IR
N-[Imino(4-methoxyphenyl)methyl]-5-methyl-2-nitrobenzamide
(7e):
Yield = 0.70 g (90%), yellow oil, Rf = 0.38 (1:1 EtOAc–hexane), IR (KBr) mmax
3434, 1656, 1524, 1213 cmÀ1 1H NMR (300 MHz, CDCl3) d = 10.56 (1H, br s,
;
(KBr) mmax 3089, 1672, 1598, 1480 cmÀ1 1H NMR (300 MHz, CDCl3+CD3OD)
;
NH), 8.09 (1H, d, J = 8.5 Hz, ArH), 7.73 (1H, s, ArH), 7.69–7.66 (1H, m, ArH),
7.38–7.36 (2H, m, ArH), 7.11–7.06 (2H, m, ArH), 6.73 (1H, br s, NH); 13C NMR
(50 MHz, CDCl3) d = 163.5, 153.0, 143.4, 131.2, 130.8, 130.6, 129.9, 129.7,
129.2, 124.8, 123.6, 114.3, 55.6, 21.5; mass (ES+) m/z 314.3 (M++1); Anal. Calcd
for C16H15N3O4: C, 61.34; H, 4.83; N, 13.41. Found: C, 61.37; H, 4.80; N, 13.43.
d = 8.02 (3H, d, J = 7.0 Hz, ArH), 7.65 (2H, d, J = 16.2 Hz, ArH), 7.05 (2H, d,
J = 6.7 Hz, CH), 3.90 (3H, s, OCH3), 2.5 (3H, s, CH3); 13C NMR (50 MHz, DMSO-d6)
d = 161.6, 135.6, 135.5, 129.2, 125.1, 124.8, 120.4, 113.8, 55.3, 20.8; mass (ES+)
m/z 267.3 (M++1); Anal. Calcd for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52.
Found: C, 72.11; H, 5.27; N, 10.53.
12. To
a
solution of N-[Imino-(4-methoxy-phenyl)-methyl]-2-nitro-benzamide
13. (a) Croce, P. D.; Ferraccioli, R.; Rosa, C. L. Heterocycles 1997, 45, 1309; (b)
Buscemi, S.; Pace, A.; Vivona, N.; Caronna, T.; Galia, A. J. Org. Chem. 1999, 64,
7028; (c) Mayer, J. P.; Lewis, G. S.; Curtis, M. J.; Zhang, J. Tetrahedron Lett. 1997,
38, 8445; (d) Dean, W. D.; Papadopoulos, E. P. J. Heterocycl. Chem. 1982, 19, 171;
(e) Gardner, B.; Kanagasooriam, A. J. S.; Smyth, R. M.; Williams, A. J. Org. Chem.
1994, 21, 6245.
(0.4 g, 0.333 mmol) in acetic acid (5 ml) under nitrogen atmosphere were
added ammonium formate (0.42 g, 1.67 mmol) and palladium on carbon 10%
wet (0.4 g) at room temperature. The reaction mixture was heated at 80 °C for
1 h. It was filtered through Celite bed and washed with ethyl acetate. The
filtrate was neutralized with satd sodium bicarbonate. The compound was
extracted with ethyl acetate (15 mL Â 3). The organic layer was washed with