Lewis acid catalyzed one-pot selective synthesis of aminobenzofurans and N -alkyl-2-aryl-2-(arylimino)acetamides: Product dependence on the nature of the aniline

Article abstract of DOI:10.1055/s-0030-1258239

An efficient one-pot reaction between isocyanides, anilines, and salicylaldehydes (2-hydroxybenzaldehydes) in the presence of a Lewis acid proceeds smoothly at room temperature within a short time interval to afford aminobenzofurans and N-alkyl-2-aryl-2-(arylimino)acetamide derivatives in high yields depending on the electron density of the aniline component. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0030-1258239

PAPER
3899
Lewis Acid Catalyzed One-Pot Selective Synthesis of Aminobenzofurans and
N-Alkyl-2-aryl-2-(arylimino)acetamides: Product Dependence on the Nature
of the Aniline
Synthesis of
A
u
minobenzof
u
d
rans and (A
i
ryl)(ary
p
limino)aceta
t
mides a Mitra, Sandip K. Hota, Partha Chattopadhyay*
Department of Chemistry, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India
Fax +91(33)24735197; E-mail: partha@iicb.res.in
Received 21 July 2010
such a methodology that would preferably require room
Abstract: An efficient one-pot reaction between isocyanides,
anilines, and salicylaldehydes (2-hydroxybenzaldehydes) in the
presence of a Lewis acid proceeds smoothly at room temperature
within a short time interval to afford aminobenzofurans and N-
temperature and shorter reaction times. We believe that
the use of an appropriate Lewis acid catalyst can improve
the reaction conditions. Hence we have investigated dif-
alkyl-2-aryl-2-(arylimino)acetamide derivatives in high yields de- ferent Lewis acid catalysts for the synthesis of the hetero-
pending on the electron density of the aniline component.
cyclic molecule.
Key words: multicomponent reaction, Lewis acids, substituent ef-
fects, cyclization, Schiff bases
In this article, we observed that the use of primary aromat-
ic amines bearing a strong electron-withdrawing group
(R2 = 2-CO2H, 3-NO2, or 4-NO2) with a salicylaldehyde
derivative and an alkyl isocyanide in ethanol containing
Multicomponent reactions (MCRs)1 have a significant im-
portance due to their exceptional synthetic efficiency.
They allow the incorporation of more than two building
blocks giving rise to complex structures in a one-pot reac-
tion. MCRs also tend to be ecofriendly by reducing the
number of synthetic steps, time consumption, and waste
production. Isocyanide-based MCRs,2 for example the
Passerini1e,3 and Ugi reactions,4 are especially important
for the construction of diverse chemical libraries of inter-
esting heterocyclic scaffolds. They are able to deliver a
wide variety of peptide analogues and heterocyclic com-
pounds for study in drug discovery programmes. The high
reactivity of isocyanides towards C(sp2 or sp) electro-
philic centers5 makes them useful reactants in organic
synthesis, especially in one-pot reactions.
cerium(IV) ammonium nitrate6 as a Lewis acid catalyst
affords aminobenzofuran derivatives in high yield (79–
85%), whereas for aniline derivatives lacking a strong
EWG the reaction takes a different course and N-alkyl-2-
aryl-2-aryliminoacetamide derivatives are obtained in
good yield (65–76%) via an oxidation step. It may be
pointed out that though many natural products7 containing
benzofuran moieties are biologically active,8,9 there are
few reports2g–i,10,11 on the synthesis of benzofuran deriva-
tives. To the best of our knowledge, this is the first one-
pot synthesis of aminobenzofuran derivatives using a
Lewis acid catalyst at low temperatures within a short re-
action time. Our method also offers an ecofriendly ap-
proach to benzofuran derivatives with varying
substitution patterns.
A few methods have been reported for the synthesis of
heterocycles utilizing isocyanides, amines, and aldehydes
in the presence of an acid catalyst,2e–h but these either re-
quire long reaction times or high temperatures to complete
the reaction. Garcia–Gonzalez et al.2f reported that MCRs
involving an aryl isocyanide, a salicylaldehyde (2-hy-
droxybenzaldehyde), and 2-aminophenol in refluxing tol-
uene containing ammonium chloride as proton source
gave benzoxazine derivatives via cyclization involving
the o-hydroxy group of the aniline component; the alter-
native benzofuran derivative was not formed. With 4-ni-
troaniline on the other hand, benzoxazine formation is not
possible and the final product is derived via elimination of
the aniline component. Ramazani et al.2g used salicylalde-
hyde derivatives and a secondary amine in the presence of
silica gel and observed the formation of iminobenzofuran
derivatives taking 24 hours. This prompted us to develop
In our initial experiments, salicylaldehyde, 4-nitroaniline,
and tert-butyl isocyanide were employed to optimize the
reaction conditions. As shown in Table 1, a series of
Lewis acid catalysts were screened and cerium(IV) am-
monium nitrate seemed to be the best choice. Using the
optimized reaction conditions, salicylaldehydes 1, aniline
derivatives containing strong electron-withdrawing sub-
stituents 2, and isocyanides 3 were reacted to produce
benzofuran derivatives 7 (Table 2). We selected 4-nitro-
aniline, 3-nitroaniline, and anthranilic acid as strong elec-
tron-deficient anilines. In the presence of the carboxylic
acid group of anthranilic acid, the desired aminobenzofu-
ran derivatives 7b–d (entries 2–4,) were formed in good
yield (82–85%) after column chromatography. The reac-
tions were complete within 35–45 minutes in the presence
of cerium(IV) ammonium nitrate (based on TLC monitor-
ing), whereas without cerium(IV) ammonium nitrate, or
any Lewis acid, reactions were very slow.
SYNTHESIS 2010, No. 22, pp 3899–3905
Advanced online publication: 01.09.2010
DOI: 10.1055/s-0030-1258239; Art ID: P11810SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
0
Interestingly, when reactions were carried out with 2-
chloroaniline, 2-bromoaniline, 2-iodoaniline, and 4-bro-
moaniline 2, isocyanides 3, and salicylaldehydes 1, we

3900
S. Mitra et al.
PAPER
Table 1 Optimization of Reaction Conditionsa
yield. Reaction with cyclohexyl isocyanide, 2-iodo-
aniline, and salicylaldehyde produced 9c in 68% yield
(entry 3), and using tert-butyl isocyanide gave 9b in 72%
yield (entry 2). Next we planned to carry out one reaction
in the presence of electron-rich salicylaldehyde and elec-
tron-deficient aniline; the reaction of o-vanillin, 3-nitro-
aniline, and tert-butyl isocyanide in presence of cerium(IV)
ammonium nitrate gave benzofuran derivative 7e (entry
5) in good (79%) yield.
Entry
Catalyst
Time (h)
Yieldb (%)
45
1
2
FeCl3
24
24
2
Cu(OAc)2
Ce(NH4)2(NO3)6 (CAN)
Zn(OAc)2
Yb(OTf)3
Er(OTf)3
n.r.c
83
3
4
24
2
n.r.c
68
5
Table 3 Synthesis of N-Alkyl-2-aryl-2-(arylimino)acetamide De-
rivativesa
6
2
65
R3
7
In(OTf)3
2
68
R2
O
NH
NH2
8
Sm(OTf)3
Y(OTf)3
2
75
CHO
OH
N
CAN
9
2
60
+
+
EtOH
R2
OH
10
11
CuBr2
24
2
n.r.c
48
9
R1
1
R1
2
CeCl3·7 H2O
R3
N C
a Reaction conditions: salicylaldehyde, 4-nitroaniline, tert-butyl iso-
cyanide, catalyst (5 mol%), EtOH (5 mL), r.t.
b Isolated yield.
3
Entry
R1
H
H
H
H
R2
R3
Product Yieldb (%)
c No reaction.
1
2
3
4
5
6
2-Cl
2-I
t-Bu
9a
9b
9c
9d
9e
9f
73
72
68
65
75
76
Table 2 Efficient Synthesis of Benzofuran Derivativesa
t-Bu
Cy
R2
2-I
NH2
HN
H
t-Bu
t-Bu
t-Bu
X
CHO
X
CAN
OMe
OMe
2-Br
4-Br
NH
R3
+
EtOH
O
OH
R2
R1
R1
+
2
7
a Reaction conditions: salicylaldehyde (1 mmol), halogenated aniline
(1 mmol), isocyanide (1 mmol), CAN (5 mol%), EtOH (5 mL), r.t., 2 h.
b Isolated yield.
1
R3
N
C
3
Entry R1
X
R2
R3
Product Yieldb
(%)
In all of the above cases the reactions were quite clean. It
should be noted that the attempted reactions with benzyl-
amine furnished only the corresponding imine with sali-
cylaldehyde and tert-butyl isocyanide; p-anisidine and p-
toluidine resulted in intractable mixtures of products.
1
2
3
4
5
H
H
H
H
4-NO2
t-Bu
t-Bu
i-Pr
7a
7b
7c
7d
7e
83
84
82
85
79
H
2-CO2H
2-CO2H
2-CO2H
3-NO2
H
Compounds 7a–e were characterized on the basis of their
H
NO2
H
t-Bu
t-Bu
1
IR, H and 13C NMR, and mass spectra and elemental
1
analysis. The H NMR spectrum of 7a consisted of one
OMe
singlet for the tert-butyl group (d = 1.32, CMe3), deuteri-
um oxide exchangeable signals for amine hydrogen atoms
(d = 5.71 and 8.37) along with appropriate chemical shifts
for the eight hydrogen atoms of the two aromatic moieties.
The 13C NMR spectrum of 7a showed 18 distinct reso-
nances, in agreement with the adduct structure. The mass
spectrum of 7a displayed a peak at m/z 348 attributed to
the [M + Na]+ ion. The 1H and 13C NMR spectra of com-
pounds 7b–e were broadly similar to those of 7a, except
for the signals for the aromatic moieties and the alkyl
groups which exhibited the expected changes in signal
patterns.
a Reaction conditions: salicylaldehyde (1 mmol), electron-deficient
aniline (1 mmol), isocyanide (1 mmol), CAN (5 mol%), EtOH (5
mL), r.t., 2 h.
b Isolated yield.
obtained the unusual adducts, N-alkyl-2-aryl-2-(arylimi-
no)acetamide derivatives 9 (Table 3). In the presence of
electron-releasing group (OMe) in the salicylaldehyde
component using 2-bromoaniline, 4-bromoaniline, com-
pounds 9e and 9f were isolated in 75% and 76% yields, re-
spectively (entries 5 and 6).
When the reaction with salicylaldehyde, aniline, and tert-
butyl isocyanide was carried out under the same condi-
tions, the unusual adduct 9d (entry 4) was formed in 65%
For compounds 9a–f, the 1H NMR spectrum of 9a consist-
ed of one singlet for the tert-butyl group (d = 1.12, CMe3),
Synthesis 2010, No. 22, 3899–3905 © Thieme Stuttgart · New York

PAPER
Synthesis of Aminobenzofurans and (Aryl)(arylimino)acetamides
3901
coupling constants indicated the presence of two aromatic
rings. The 13C NMR spectrum of 9a showed 18 distinct
peaks and the mass spectrum displayed the molecular ion
peak [M]+ at m/z 330. Finally single crystal X ray
analysis12 of 9a conclusively confirmed its structure
(Figure 1).
The data shows that the bond distance for C7–N1 is 1.286
Å, in agreement with the values reported for a C=N
bond.2f It is of considerable importance that the crystal
structure of 9a shows one intramolecular interaction be-
tween O2–H2⋅⋅⋅N1 with distance 1.79 Å.2f This proximity
is fully consistent with the strong deshielding of H2
(d = 12.79) found in the 1H NMR spectrum of 9a. The 1H
and 13C NMR spectra of compounds 9b–f were similar to
those of 9a.
Although the mechanism of the above reactions has not
been established, a possible one is outlined in Scheme 1.2e
Initially the carbonyl group of 1 is activated by coordina-
tion of the oxygen atom with cerium(IV) ammonium ni-
trate facilitating the formation of the 2-(arylimino)phenol,
which is also activated by cerium(IV) ammonium nitrate.
Thereafter, nucleophilic addition of isocyanides 3 pro-
duces the intermediate 4 which is stabilized and confor-
mationally locked by intramolecular hydrogen bonding,
unless electron density around the aromatic amine nitro-
gen atom is reduced by a strong deactivating substituent
(NO2, CO2H). In the conformation 4, the adjacent hydroxy
group cannot participate in intramolecular cyclization. As
a consequence, addition of water13 could result in adduct
Figure 1 ORTEP diagram of compound 9a
one amide proton signal (d = 5.48) and one sharp singlet
at d = 12.79 which indicate the presence of the chelated
phenolic OH group. Signals for eight hydrogen atoms
with appropriate chemical shifts (d = 6.90 to 7.55) and
R2
R2
R2
HN
HN
O
HN
X
X
X
NHR3
N
N
R3
R3
••
O
OH
R1
R1
R1
6
5
7
when R2 = NO2, COOH
R3
N
R2
3
R2
NH2
R3
N C
X
CHO
OH
X
H
CAN
X
+
N
N
EtOH
H
R2
R1
1
OH
H
O
R1
4
2
R1
when R2 = H, Cl, Br, I
H2O
R3
R3
R2
R2
O
NH
O
NH
aerial oxidation
X
X
N
H
N
OH
OH
R1
R1
9
8
Scheme 1 Proposed mechanism for the synthesis of benzofurans and N-alkyl-2-aryl-2-(arylimino)acetamide derivatives
Synthesis 2010, No. 22, 3899–3905 © Thieme Stuttgart · New York

3902
S. Mitra et al.
PAPER
Anal. Calcd for C18H19N3O3: C, 66.45; H, 5.89; N, 12.91. Found: C,
66.27; H, 6.11; N, 13.12.
8 and this produces the final product 9 upon aerial oxida-
tion.
When R2 = 2-CO2H, 3-NO2, 4-NO2, i.e. in the presence of
a strong electron-withdrawing substituent, poor electron
density around aromatic amine nitrogen atom discourages
the formation of an intramolecular hydrogen bond. Thus
C–C bond rotation (as shown in 4, Scheme 1) could result,
leading to conformer 5, which would generate 6 through
intramolecular cyclization. Subsequent tautomerization
could then lead to final product 7.
2-(tert-Butylamino)-7-methoxy-3-(3-nitrophenylamino)benzo-
furan (7e)
Yellow powder; mp 163–166 °C; Rf = 0.67 (PE–EtOAc, 4:1).
IR (KBr): 3316, 2967, 1625, 1527, 1475, 1348, 1303, 1203, 1087,
730 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 1.29 (s, 9 H), 3.93 (s, 3 H),
5.48 (s, 1 H), 6.56 (d, J = 7.5 Hz, 1 H), 6.71 (d, J = 7.8 Hz, 1 H),
6.96–7.02 (m, 2 H), 7.32–7.45 (m, 3 H), 7.67 (s, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 30.1 (3 CH3), 52.7 (C), 55.8
(CH), 98.7 (C), 104.5 (CH), 106.6 (CH), 108.9 (CH), 111.1 (CH),
119.4 (CH), 123.4 (CH), 129.2 (C), 130.0 (CH), 137.0 (C), 144.1
(C), 148.7 (C), 149.0 (C), 153.9 (C).
In conclusion, we have developed an efficient, one-pot
synthesis of benzofurans and the unusual N-alkyl-2-aryl-
2-(arylimino)acetamide derivatives from readily available
isocyanides 3, salicylaldehyde or substituted analogues 1,
and substituted anilines 2 in the presence of a Lewis acid
at room temperature.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H21N3O4: 378.1430;
found: 378.1469.
Anal. Calcd for C19H21N3O4: C, 64.21; H, 5.96; N, 11.82. Found: C,
64.09; H, 6.09; N, 11.64.
The ease of purification, fairly short reaction times and
good yields of the products make this procedure a useful
addition to modern organic synthesis. Our methodologies
also offer more opportunities for further functionalization.
(Benzofuran-3-ylamino)benzoic Acids 7b–d; General Proce-
dure
To a soln of salicylaldehyde 1 (1 mmol) and anthranilic acid 2 (1
mmol) in EtOH (5 mL) was added CAN (5 mol%) immediately fol-
lowed by isocyanide 3 (1 mmol). The mixture was stirred at r.t. for
1 h. The solvent was removed via rotary evaporation. To the mix-
ture was added H2O (10 mL) and then it was extracted with CH2Cl2
(2 × 10 mL). The organic layers were combined, dried (Na2SO4), fil-
tered, and concentrated. The crude residue was purified via column
chromatography (silica gel, 100–200 mesh) to give 7b–d.
Reaction at r.t. generally implies a temperature of 25 °C. Some re-
agents were obtained from commercial sources and used without
purification. The solvents used were of technical grade, and freshly
distilled prior to use. All melting points were obtained on a labora-
tory devices melting point bath and are uncorrected. 1H (300 MHz,
600 MHz) and 13C (75 MHz, 150 MHz) NMR spectra were recorded
using CDCl3 and DMSO-d6 with TMS as internal standard on Bruker
DPX 300 MHz and Bruker DRX 600 MHz NMR instruments at r.t.
IR spectra were recorded on a Jasco-FTIR Model-410, using KBr
pellets. Mass spectra were measured in ESIMS (+), EIMS, FAB-
MS, and HRMS mode. DI-EIMS were recorded on a GCMS-
Shimadzu-QP5050A and ESIMS were done on a Waters Micro-
mass Q-TOF microTM Mass Spectrometer. X-ray crystallographic
data of single crystals were collected on Bruker Kappa Apex II with
Mo-Ka radiation (l = 0.71073 Å). TLC was performed on pre-coated
plates (0.25 nm, silica gel 60 F254). PE = petroleum ether.
2-[2-(tert-Butylamino)benzofuran-3-ylamino]benzoic Acid (7b)
Brown powder; mp 178–181 °C; Rf = 0.27 (PE–EtOAc, 4:1).
IR (KBr): 3337, 2967, 1665, 1455, 1387, 1260, 744 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 1.29 (s, 9 H), 5.62 (s, 1 H),
6.46 (d, J = 6.6 Hz, 1 H), 6.67 (br s, 1 H), 6.90–6.91 (d-like, 1 H),
7.04 (s, 2 H), 7.27 (br s, 1 H), 7.37–7.39 (d-like, 1 H), 7.88 (br s, 1
H), 8.83 (br s, 1 H), 12.84 (br s, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 30.2 (3 CH3), 52.8 (C), 98.4
(C), 110.2 (CH), 113.4 (CH), 115.8 (CH), 116.2 (CH), 120.6 (CH),
122.6 (CH), 127.6 (C), 131.6 (CH), 134.0 (CH), 148.7 (C), 150.2
(C), 154.1 (C), 170.2 (C).
2-(tert-Butylamino)-3-(nitrophenylamino)benzofurans 7a and
7e; General Procedure
To a stirred soln of salicylaldehyde or o-vanillin 1 (1 mmol) and ni-
troaniline 2 (1 mmol) in EtOH (5 mL) was added CAN (5 mol%)
immediately followed by isocyanide 3 (1 mmol). The mixture was
stirred at r.t. for 2 h and a yellow solid precipitated; this was filtered
and washed with the minimum amount of EtOH. The filtrate was
evaporated in vacuo and the solid was triturated (CH2Cl2 and hex-
ane) to give a solid product which was combined with the previous
yellow solid residue.
MS (EI): m/z = 324.
Anal. Calcd for C19H20N2O3: C, 70.35; H, 6.21; N, 8.64. Found: C,
70.54; H, 6.43; N, 8.55.
2-[2-(Isopropylamino)benzofuran-3-ylamino]benzoic Acid (7c)
Yellow amorphous solid; mp 163–166 °C; Rf = 0.29 (PE–EtOAc,
4:1).
IR (KBr): 3338, 2968, 1671, 1645, 1575, 1455, 1260, 742 cm–1.
2-(tert-Butylamino)-3-(4-nitrophenylamino)benzofuran (7a)
Yellow powder; mp 162–165 °C; Rf = 0.62 (PE–EtOAc, 4:1).
1H NMR (300 MHz, DMSO-d6): d = 1.13 (d, J = 6.3 Hz, 6 H), 3.79–
3.86 (m, 1 H), 6.42 (dd, J = 8.7, 13.2 Hz, 1 H), 6.64 (t, J = 7.3 Hz,
1 H), 6.82 (d, J = 7.2 Hz, 1 H), 6.90–6.95 (t-like, 1 H), 6.99–7.04 (t-
like, 1 H), 7.27 (dd, J = 7.8, 14.7 Hz, 2 H), 7.86 (d, J = 7.5 Hz, 1 H),
8.74 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 23.9 (2 CH3), 45.8 (CH), 93.5 (C),
109.6 (C), 110.0 (CH), 113.9 (CH), 115.9 (CH), 116.4 (CH), 120.1
(CH), 122.9 (CH), 128.8 (C), 132.4 (CH), 135.7 (CH), 149.0 (C),
151.5 (C), 154.2 (C), 173.8 (C).
IR (KBr): 3290, 2968, 1597, 1492, 1337, 1190, 1109, 835, 740
cm–1.
1H NMR (300 MHz, DMSO-d6): d = 1.32 (s, 9 H), 5.71 (s, 1 H),
6.64 (d, J = 8.7 Hz, 2 H), 6.92 (d, J = 6.9 Hz, 1 H), 7.00–7.11 (m, 2
H), 7.39 (d, J = 7.5 Hz, 1 H), 8.04 (d, J = 9.0 Hz, 2 H), 8.37 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 30.4 (3 CH3), 53.6 (C), 96.3 (C),
110.5 (CH), 112.4 (2 CH), 116.0 (CH), 120.9 (CH), 123.0 (CH),
126.2 (2 CH), 127.0 (C), 139.1 (C), 149.2 (C), 152.8 (C), 155.0 (C).
MS (EI): m/z = 310.
MS (ESI): m/z = 348 [M + Na]+.
Anal. Calcd for C18H18N2O3: C, 69.66; H, 5.85; N, 9.03. Found: C,
69.50; H, 5.98; N, 8.87.
Synthesis 2010, No. 22, 3899–3905 © Thieme Stuttgart · New York

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Synthesis of Aminobenzofurans and (Aryl)(arylimino)acetamides
3903
2-[2-(tert-Butylamino)-5-nitrobenzofuran-3-ylamino]benzoic
IR (KBr): 3229, 3069, 2930, 2853, 1631, 1194, 754 cm–1.
Acid (7d)
1H NMR (300 MHz, CDCl3): d = 0.79–0.90 (m, 2 H), 1.06–1.13 (m,
1 H), 1.19–1.30 (m, 2 H), 1.51 (d, J = 8.7 Hz, 4 H), 1.59 (s, 1 H),
3.74 (dd, J = 9.9, 18.9 Hz, 1 H), 5.47 (d, J = 8.1 Hz, 1 H), 6.93 (t,
J = 7.7 Hz, 2 H), 7.08 (t, J = 8.3 Hz, 2 H), 7.36 (t, J = 7.4 Hz, 1 H),
7.44 (t, J = 7.5 Hz, 1 H), 7.54 (d, J = 7.8 Hz, 1 H), 7.86 (d, J = 8.1
Hz, 1 H), 12.72 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 24.3 (CH2), 25.1 (2 CH2), 32.2
(2 CH2), 48.0 (CH), 91.5 (C), 115.6 (C), 118.2 (CH), 119.2 (CH),
121.4 (CH), 127.2 (CH), 129.4 (CH), 131.1 (CH), 134.4 (CH),
138.5 (CH), 148.9 (C), 161.2 (C), 162.2 (C), 168.9 (C).
Brown amorphous solid; mp 205–208 °C; Rf = 0.16 (PE–EtOAc,
4:1),
IR (KBr): 3368, 2973, 1650, 1516, 1340, 1255, 749 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 1.36 (s, 9 H), 6.43–6.48 (m, 2
H), 6.73 (br s, 1 H), 7.28–7.30 (m, 1 H), 7.59–7.62 (m, 2 H), 7.89
(dd, J = 2.1, 8.7 Hz, 2 H), 8.83 (br s, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 30.2 (3 CH3), 52.9 (C), 95.0
(C), 110.1 (CH), 110.5 (CH), 113.1 (CH), 115.7 (CH), 116.2 (CH),
129.2 (C), 131.8 (CH), 134.2 (CH), 143.7 (C), 149.9 (C), 151.7 (C),
157.6 (C), 170.1 (C).
MS (FAB+): m/z = 449.
MS (FAB+): m/z = 369.
Anal. Calcd for C20H21IN2O2: C, 53.58; H, 4.72; N, 6.25. Found: C,
53.36; H, 4.89; N, 6.03.
Anal. Calcd for C19H19N3O5: C, 61.78; H, 5.18; N, 11.38. Found: C,
62.05; H, 4.93; N, 11.12.
N-tert-Butyl-2-(2-hydroxyphenyl)-2-(phenylimino)acetamide
(9d)
Grey solid; mp 169–172 °C; Rf = 0.53 (PE–EtOAc, 4:1),
IR (KBr): 3286, 1644, 1603, 1567, 1226, 1192, 754 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.16 (s, 9 H), 5.21 (s, 1 H), 6.91
(t, J = 7.3 Hz, 1 H), 7.02 (d, J = 8.4 Hz, 1 H), 7.13 (d, J = 7.5 Hz, 2
H), 7.22 (t-like, 1 H), 7.37 (t-like, 3 H), 7.52 (d, J = 7.8 Hz, 1 H),
13.29 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 28.2 (3 CH3), 52.3 (C), 116.2 (C),
117.8 (CH), 118.9 (CH), 121.3 (2 CH), 125.8 (CH), 128.9 (2 CH),
130.6 (CH), 133.7 (CH), 146.4 (C), 161.9 (C), 162.3 (C), 168.1 (C).
(Phenylimino)acetamides 9a–f; General Procedure
To a soln of salicylaldehyde 1 (1 mmol) and aniline 2 (1 mmol) in
EtOH (5 mL) was added CAN (5 mol%) immediately followed by
isocyanide 3 (1 mmol). The mixture was stirred at r.t. for 3–4 h. The
solvent was removed via rotary evaporation and the crude product
was crystallized (CH2Cl2–hexane) to give 9a–f.
N-tert-Butyl-2-(2-chlorophenylimino)-2-(2-hydroxyphen-
yl)acetamide (9a)
Yellow solid; mp 155–158 °C; Rf = 0.57 (PE–EtOAc, 4:1).
IR (KBr): 3290, 3059, 2978, 1663, 1601, 1552, 1449, 1208, 883,
758 cm–1.
MS (EI): m/z = 296.
1H NMR (300 MHz, CDCl3): d = 1.12 (s, 9 H), 5.48 (s, 1 H), 6.94
(t, J = 7.7 Hz, 1 H), 7.05 (d, J = 8.4 Hz, 1 H), 7.12–7.19 (m, 2 H),
7.28–7.30 (m, 1 H), 7.44 (t, J = 7.7 Hz, 2 H), 7.54 (d, J = 7.8 Hz, 1
H), 12.79 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 28.2 (3 CH3), 52.4 (C), 115.8 (C),
118.2 (CH), 119.1 (CH), 122.8 (CH), 125.6 (C), 126.6 (CH), 127.7
(CH), 129.3 (CH), 131.0 (CH), 134.4 (CH), 144.4 (C), 161.6 (C),
162.2 (C), 169.5 (C).
Anal. Calcd for C18H20N2O2: C, 72.95; H, 6.80; N, 9.45. Found: C,
73.19; H, 6.56; N, 9.22.
2-(2-Bromophenylimino)-N-tert-butyl-2-(2-hydroxy-3-meth-
oxyphenyl)acetamide (9e)
Yellow solid; mp 170–173 °C; Rf = 0.36 (PE–EtOAc, 4:1),
IR (KBr): 3320, 3064, 2969, 1671, 1602, 1538, 1460, 1258, 1205,
1024, 855, 742 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.12 (s, 9 H), 3.94 (s, 3 H), 5.47
(s, 1 H), 6.88 (d, J = 7.8 Hz, 1 H), 7.03–7.18 (m, 4 H), 7.33 (t-like,
1 H), 7.63 (d, J = 7.8 Hz, 1 H), 13.12 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 28.0 (3 CH3), 52.4 (C), 56.0 (CH3),
115.3 (CH), 115.5 (C), 115.7 (C), 118.4 (CH), 122.2 (CH), 122.5
(CH), 126.8 (CH), 128.1 (CH), 132.2 (CH), 145.4 (C), 148.6 (C),
152.3 (C), 161.5 (C), 169.2 (C).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H19ClN2NaO2:
353.1033; found: 353.1068.
Anal. Calcd for C18H19ClN2O2: C, 65.35; H, 5.79; N, 8.47. Found:
C, 65.12; H, 5.98; N, 8.25.
N-tert-Butyl-2-(2-hydroxyphenyl)-2-(2-iodophenylimino)acet-
amide (9b)
Off-white solid; mp 164–168 °C; Rf = 0.57 (PE–EtOAc, 4:1).
MS (EI): m/z = 404, 406.
IR (KBr): 3264, 3069, 2965, 1633, 1605, 1554, 1454, 1195, 753
cm–1.
Anal. Calcd for C19H21BrN2O3: C, 56.31; H, 5.22; N, 6.91. Found:
C, 56.57; H, 5.48; N, 7.07.
1H NMR (300 MHz, CDCl3): d = 1.11 (s, 9 H), 5.43 (s, 1 H), 6.94
(t, J = 7.2 Hz, 2 H), 7.08 (dd, J = 8.1, 14.1 Hz, 2 H), 7.36 (t, J = 7.7
Hz, 1 H), 7.44 (t, J = 7.7 Hz, 1 H), 7.56 (d, J = 7.8 Hz, 1 H), 7.88 (d,
J = 7.8 Hz, 1 H), 12.69 (s, 1 H).
2-(4-Bromophenylimino)-N-tert-butyl-2-(2-hydroxy-3-meth-
oxyphenyl)acetamide (9f)
Light yellow solid; mp 173–176 °C; Rf = 0.30 (PE–EtOAc, 2:1).
13C NMR (CDCl3, 150 MHz): d = 28.2 (3 CH3), 52.5 (C), 91.2 (C),
115.6 (C), 118.2 (CH), 119.2 (CH), 121.8 (CH), 127.0 (CH), 129.3
(CH), 131.1 (CH), 134.4 (CH), 138.4 (CH), 149.0 (C), 161.5 (C),
162.2 (C), 169.0 (C).
IR (KBr): 3318, 3070, 2958, 1670, 1588, 1530, 1458, 1250, 1196,
1022, 854, 740 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.23 (s, 9 H), 3.89 (s, 3 H), 5.52
(s, 1 H), 6.85 (d-like, 1 H), 6.96–7.12 (m, 4 H), 7.48 (d, J = 8.1 Hz,
1 H), 13.56 (s, 1 H).
MS (EI): m/z = 422.
13C NMR (75 MHz, CDCl3): d = 28.0 (3 CH3), 51.3 (C), 56.0 (CH3),
115.9 (CH), 116.3 (C), 118.0 (C), 118.4 (CH), 121.9 (CH), 123.8
(2 CH), 131.5 (2 CH), 145.6 (C), 148.5 (C), 151.8 (C), 161.4 (C),
169.3 (C).
Anal. Calcd for C18H19IN2O2: C, 51.20; H, 4.54; N, 6.63. Found: C,
50.98; H, 4.36; N, 6.42.
N-Cyclohexyl-2-(2-hydroxyphenyl)-2-(2-iodophenylimino)acet-
amide (9c)
Yellow solid; mp 170–173 °C; Rf = 0.55, (PE–EtOAc, 4:1).
MS (ESI+): m/z = 404, 406, 427 [M + Na]+.
Synthesis 2010, No. 22, 3899–3905 © Thieme Stuttgart · New York

3904
S. Mitra et al.
PAPER
R.; Rosario Torres, M. Eur. J. Org. Chem. 2010, 823.
(i) Sridharan, V.; Menéndez, J. C. Chem. Rev. 2010, 110,
3805.
Anal. Calcd for C19H21BrN2O3: C, 56.31; H, 5.22; N, 6.91. Found:
C, 56.06; H, 4.99; N, 7.10.
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Acknowledgment
Financial support from the Department of Science and Technology
(DST), New Delhi, Government of India is gratefully acknowled-
ged. We thank CSIR (India) for financial assistance. Thanks are
also due to Dr. B. Achari, Emeritus Scientist, IICB, for valuable
suggestions.
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(12) Crystal data of compound 10a: C18H19ClN2O2,
FW = 330.80, monoclinic, space group P21/c, a = 12.0348
(13) Å, b = 18.050 (2) Å, c = 7.9752 (9) Å, b = 102.269 (5)°,
V = 1692.9 (3) Å3, Z = 4, T = 296 (2) K, dcalcd = 1.298 g cm–3,
F(000) = 696. Diffraction data were measured with MoKa
Synthesis 2010, No. 22, 3899–3905 © Thieme Stuttgart · New York

PAPER
Synthesis of Aminobenzofurans and (Aryl)(arylimino)acetamides
3905
(l = 0.71073 Å) radiation at 296 K using a Bruker Kappa
wR2 = 0.1202 with I > 2s(I). Crystallographic data have
been deposited at the Cambridge Crystallographic Data
Centre with reference number CCDC 773605.
Apex 2 CCD system. A total of 2404 unique reflections were
measured (qmax = 25.00°). Data analyses were carried out
with the Fast Fourier Transform program. The structures
were solved by direct methods using the SHELXS-9714
program. Refinements were carried out with a full matrix
least squares method against F2 using SHELXL-97.15 Non-
hydrogen atoms were refined with anisotropic thermal
parameters. The final R value was R1 = 0.0375 and
(13) Yavari, I.; Djahaniani, H. Tetrahedron Lett. 2006, 47, 1477.
(14) (a) Program for solution of crystal structures: Sheldrick, G.
M. SHELXS-97; University of Göttingen: Germany, 1997.
(b) Sheldrick, G. M. Acta Crystallogr., Sect. A 1990, 46, 467.
(15) Program for refinement of crystal structures: Sheldrick, G.
M. SHELXL-97; University of Göttingen: Germany, 1997.
Synthesis 2010, No. 22, 3899–3905 © Thieme Stuttgart · New York