A new, one-pot, three-component, solvent-free synthesis of amidoalkyl dibenzofuranols and dibenzofuran-condensed 1,3-oxazin-3-ones

Article abstract of DOI:10.1055/s-0029-1218624

A new, one-pot, three-component synthesis of amido-alkyl dibenzofuranols and dibenzofuran-condensed 1,3-oxazin-3-ones in good to excellent yields via the reaction of dibenzofuran-2-ol, an aromatic aldehyde, and an amide or urea in the presence of tin(II) chloride dihydrate as a Lewis acid catalyst is described. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0029-1218624

PAPER
959
A New, One-Pot, Three-Component, Solvent-Free Synthesis of Amidoalkyl
Dibenzofuranols and Dibenzofuran-Condensed 1,3-Oxazin-3-ones
Synthesis of
D
r
ibenzofu
i
ranol
D
n
e
rivatives ivas Kantevari,* Thirumal Yempala, Srinivasu V. N. Vuppalapati
Organic Chemistry Division-II, Indian Institute of Chemical Technology, Hyderabad 500007, India
E-mail: kantevari@yahoo.com; E-mail: kantevari@gmail.com
Received 6 October 2009; revised 20 November 2009
The dibenzofuran unit is the basic structural framework of
several natural products with pronounced biological prop-
erties;8 examples include fulicineroside, lucidafuran,
eriobofuran, cannabifuran, ruscodibenzofuran and karna-
takafurans. Simple dibenzofurans also occur in higher
plants where they often act as antifungal phytoalexins.9
Synthetic heterocycles derived from dibenzofuran display
important and therapeutically useful biological activity
such as antibacterial, antidepressant and antitubercular.9
We envisaged that the preparation of heterocycles con-
taining amidoalkyl and 1,3-oxazin-3-one groups on a
dibenzofuran system, as possible drug-like candidates,
would be of synthetic importance. We herein describe our
investigations of a novel, one-pot, multicomponent, sol-
vent-free condensation of dibenzofuran-2-ol (4), various
aromatic aldehydes, and an amide or urea in the presence
of a Lewis or protic acid catalyst. To the best of our
knowledge, this is the first report on the synthesis of
amidoalkyl dibenzofuranols 6a–n and dibenzofuran-
condensed 1,3-oxazin-3-ones 7a–e.
Abstract: A new, one-pot, three-component synthesis of amido-
alkyl dibenzofuranols and dibenzofuran-condensed 1,3-oxazin-3-
ones in good to excellent yields via the reaction of dibenzofuran-2-
ol, an aromatic aldehyde, and an amide or urea in the presence of
tin(II) chloride dihydrate as a Lewis acid catalyst is described.
Key words: dibenzofuran, multicomponent reaction, amidoalkyl
dibenzofuranol, 1,3-oxazin-3-ones, solvent-free, condensation re-
actions, aromatic aldehyde
Reactions that generate carbon–carbon bonds, and at the
same time introduce nitrogen-containing functionalities
into a structural framework, are especially attractive for
the rapid construction of organic molecules.1 In recent
years, the application of logic-based single reactant re-
placement (SRR) as a means to improve both known mul-
ticomponent reactions, and to design new routes to
potentially bioactive complex structures has gained mo-
mentum.2 In this context, the procedure for the synthesis
of naphthalene-condensed heterocycles such as dibenzo-
xanthenes 1,3 amidoalkyl naphthols 24 and naphthoxazin-
3-ones 3,5 via the one-pot, three-component condensation
of 2-naphthol, an aldehyde and an amide or urea, was of
interest to us6 for appropriate modification using similar,
but more bioactive components as substrates.7
The starting substrate for the study, dibenzofuran-2-ol (4)
was prepared from dibenzofuran according to the litera-
ture procedure,10 and was fully characterized by spectro-
scopic analysis.
Initially, efforts were focused on the reaction of dibenzo-
furan-2-ol (4), p-chlorobenzaldehyde (5b) and acetamide
with various Lewis and protic acid catalysts (Table 1).
The yields of amidoalkyl dibenzofuranol 6b, which was
obtained as racemic mixture, are shown in Table 1. The
reaction proceeded efficiently with tin(II) chloride dihy-
drate (SnCl2·2H2O) under solvent-free conditions (3.5
hours, 125 °C) to give the corresponding amidoalkyl
dibenzofuranol 6b in 96% yield (entry 14, Table 1). It was
found that the mole ratio of tin(II) chloride dihydrate in-
fluenced the yield of the product, with 20 mol% being op-
timum. Furthermore, no product was detected in the
absence of a catalyst. Investigation of the reaction temper-
ature indicated that 125 °C was the most favorable for the
formation of 6b.
R
OH
NHCOR1
R2
O
1
2
O
N
O
H
R
3
In order to study the general scope and versatility of this
procedure for the synthesis of a series of substituted ami-
doalkyl dibenzofuranols 6, the condensation of dibenzo-
furan-2-ol (4), aldehydes 5a–m, and acetamide,
benzamide or urea was examined. The three-component
reaction of aryl aldehydes bearing electron-withdrawing
or electron-donating substituents proceeded smoothly to
give the desired amidoalkyl dibenzofuranols 6a–n in good
Figure 1 Examples of naphthalene-condensed heterocycles
SYNTHESIS 2010, No. 6, pp 0959–0966
Advanced online publication: 08.01.2010
DOI: 10.1055/s-0029-1218624; Art ID: Z21009SS
x
x
.
x
x
.2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

960
S. Kantevari et al.
PAPER
Table 1 Catalyst Optimizationa
aldehyde (5m) (entries 17 and 18, Table 2) did not react
with dibenzofuran-2-ol (4) and acetamide under the opti-
mized conditions, nor with any of the catalysts specified
in Table 1. Therefore, no additional aliphatic aldehydes
were tested. The reaction was also unsuccessful with the
sugars D-glucose and L-rhamnose (entries 15 and 16,
Table 2).
Cl
CHO
OH
NHCOMe
OH
MeCONH2
+
catalyst
O
O
Cl
4
5b
6b
Encouraged by the results obtained with aromatic alde-
hydes, we extended this protocol to the one-pot, three-
component synthesis of dibenzofuran-condensed 1,3-ox-
azin-3-ones 7. Condensation of 4 with various aromatic
aldehydes and urea at elevated temperature (160 °C) gave
1,3-oxazin-3-ones 7a–e in excellent yields (Table 3). In a
typical example, reaction of dibenzofuran-2-ol (4), p-
chlorobenzaldehyde (5b) and urea in the presence of
tin(II) chloride dihydrate (20 mol%) at 160 °C for 2.5
hours gave product 7a in 95% yield (entry 1, Table 3).
Under these conditions, the corresponding amidoalkyl
dibenzofuranol 6c was not present according to thin layer
chromtography. Decreasing the temperature (135 °C) re-
sulted in formation of both amidoalkyl dibenzofuranol 6c
and 1,3-oxazin-3-one 7a in variable yields, even after an
extended reaction time (24 hours). This result indicated
that the amidoalkyl dibenzofuranol 6 is formed first and
then undergoes dehydration–cyclization to give the 1,3-
oxazin-3-one 7. Products 6a–n and 7a–e were fully char-
acterized by IR and NMR spectroscopy, and by mass
spectrometry.
Entry Catalyst
mol%
Time (h) Yield (%)b
1
AcOH
excess
(solvent)
12
35
2
3
p-TSA
100
30
30
30
30
20
30
20
20
30
30
30
20
3.5
48
85
82
65
68
56
63
76
72
45
48
46
96
68
40
82
96
HClO4–SiO2
H2SO4–SiO2
InCl3
3.5
3.5
8
4
5
6
I2
4
7
BiCl3
12
8
CuCl2·4H2O
Bi(OTf)3
Zn(OTf)2
FeCl3
9
9
4.5
4.5
10
11
12
13
14
15
16
17
18
10
LiBr
12
4
CoCl2
A plausible mechanism for the formation of amidoalkyl
dibenzofuranols 6 and 1,3-oxazin-3-ones 7 is illustrated in
Scheme 1. On the basis of the established chemistry of
tin(II) chloride catalyzed organic reactions, and a similar
process in the literature,5 it is reasonable to assume that
ortho-quinone methide 9 is formed initially via addition of
dibenzofuran-2-ol (4) to the aromatic aldehyde 5 and sub-
sequent dehydration in the presence of the acidic catalyst.
Next, Michael addition of the amide or urea leads to the
formation of amidoalkyl dibenzofuranol 6. At elevated
temperature, dehydration takes place to give dibenzofu-
ran-condensed oxazin-3-one 7.
SnCl2·2H2O
3.5
Montmorillonite-K10 20
3.5
6
K5CoW12O40·3H2O
SnCl2·2H2O
20
10
30
3.5
3.5
SnCl2·2H2O
a Dibenzofuran-2-ol (4) (1 mmol), p-chlorobenzaldehyde (5b) (1
mmol), acetamide (1 mmol) and catalyst were heated at 125 °C.
b Yield of isolated product 6b.
to excellent yields (Table 2). As expected, aromatic alde-
hydes possessing electron-withdrawing groups reacted
faster than those with electron-donating groups. A large
number of aryl aldehydes are readily available, hence this
three-component reaction may be useful for the synthesis
of various other amidoalkyl dibenzofuranols.
R1
R1
OH
OH
O
4
+
5
catalyst
O
O
9
8
This three-component reaction was also carried out using
the heteroaromatic aldehydes furfural and indole-3-car-
boxaldehyde (entries 13 and 14, Table 2). The reaction
proceeded well with furfural (5h) (entry 13, Table 2) giv-
ing a 72% yield of the expected product. However, the re-
action with indole-3-carboxaldehyde (5i) (entry 14,
Table 2) was sluggish resulting in the formation of 6n in
a poor yield along with several unidentified by-products.
The aliphatic aldehydes isobutyraldehyde (5l) and valer-
O
NHCOR2
OH
H
R1
R1
N
O
O
O
7
6
Scheme 1 A plausible mechanism for the formation of amidoalkyl
dibenzofuranol 6 and its 1,3-oxazin-3-one analogue 7
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Synthesis of Dibenzofuranol Derivatives
961
Table 2 Synthesis of Amidoalkyl Dibenzofuranols 6a–n
Entry
1
Aldehyde
Amide/Urea
Producta
Time (h) Yield (%)b
NHCOMe
OH
5a
MeCONH2
6a
4.5
3.5
3.5
3.5
80
96
93
91
CHO
O
Cl
Cl
Cl
NHCOMe
OH
2
3
4
5b
5b
5b
MeCONH2
NH2CONH2
PhCONH2
6b
6c
6d
CHO
CHO
CHO
Cl
Cl
Cl
O
O
O
NHCONH2
OH
NHCOPh
OH
MeO
MeO
MeO
MeO
MeO
MeO
MeO
NHCOMe
OH
5
6
7
5c
5c
5c
MeCONH2
PhCONH2
NH2CONH2
6e
6f
6
6
6
85
82
85
CHO
MeO
O
O
O
MeO
MeO
MeO
NHCOPh
OH
CHO
MeO
MeO
MeO
MeO
NHCONH2
OH
6g
CHO
MeO
MeO
MeO
Br
NHCONH2
OH
8
9
5d
5e
NH2CONH2
MeCONH2
6h
6i
4
4
90
82
CHO
Br
O
Br
NHCOMe
OH
CHO
Br
O
Synthesis 2010, No. 6, 959–966 © Thieme Stuttgart · New York

962
S. Kantevari et al.
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Table 2 Synthesis of Amidoalkyl Dibenzofuranols 6a–n (continued)
Entry
10
Aldehyde
Amide/Urea
MeCONH2
Producta
Time (h) Yield (%)b
MeO
MeO
NHCOMe
OH
5f
6j
5
5
88
83
CHO
CHO
MeO
MeO
O
O
NHCONH2
OH
11
5f
NH2CONH2
6k
NHCOMe
OH
12
13
5g
5h
MeCONH2
MeCONH2
6l
5
7
78
72
CHO
O
NHCOMe
OH
O
6m
CHO
O
O
CHO
NHCOMe
OH
HN
14
5i
MeCONH2
6n
7
35
N
H
O
HOH2C
HO
O
15
16
5j
MeCONH2
MeCONH2
no reaction
no reaction
24
24
–
–
HO
OH
OH
OH
5k
O
HO
HO
OH
17
18
5l
MeCONH2
MeCONH2
no reaction
no reaction
24
24
–
–
CHO
CHO
5m
a All reactions were performed in the presence of SnCl2·2H2O (20 mol%) at 125 °C under solvent-free conditions.
b Yield of isolated product.
In conclusion, we have described the synthesis of novel excellent yields. The products may show potential as
amidoalkyl dibenzofuranols 6a–n and dibenzofuran-con- drug-like candidates.
densed 1,3-oxazin-3-ones 7a–e through an efficient one-
pot, three-component condensation of dibenzofuran-2-ol
Melting points were measured with a Fischer-Johns melting point
(4), aromatic aldehydes 5, and an amide or urea under sol-
vent-free conditions. Among the catalysts examined,
tin(II) chloride dihydrate proved to be the most effective
for this transformation. The described procedure is simple
and the products are easily isolated and purified in good to
apparatus and are uncorrected. IR spectra were recorded on a
Perkin-Elmer spectrophotometer. NMR spectra were recorded on
Bruker (1H NMR, 300 MHz; 13C NMR, 75 MHz) and Varian (1H
NMR, 500 MHz) spectrometers with DMSO-d6, CDCl3 or a mixture
of CDCl3–DMSO-d6 (8:2) and with tetramethylsilane as the internal
standard. Low-resolution mass spectra were obtained using electron
impact (EI), and high-resolution mass spectra (HRMS) were record-
Synthesis 2010, No. 6, 959–966 © Thieme Stuttgart · New York

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Synthesis of Dibenzofuranol Derivatives
963
Table 3 Synthesis of Dibenzofuran-Condensed 1,3-Oxazin-3-ones 7a–e
R
O
H
N
CHO
OH
NH2CONH2
O
+
SnCl2⋅2H2O
O
R
O
4
5
7
Entry
1
Aldehyde
Producta
Time (h)
Yield (%)b
O
H
N
Cl
Br
O
5b
7a
2.5
95
92
90
89
CHO
CHO
Cl
O
O
O
H
N
O
2
3
4
5d
5n
5f
7b
7c
7d
3
Br
O
H
N
O
2.5
CHO
O
O
H
MeO
N
O
3
CHO
MeO
O
MeO
MeO
MeO
MeO
O
H
N
MeO
5
5c
7e
4
85
CHO
O
MeO
O
a All reactions were performed in the presence of SnCl2·2H2O (20 mol%) at 160 °C under solvent-free conditions.
b Yield of isolated product.
ed using electrospray ionization (ESI) on an ESI-QTOF mass spec-
trometer.
N-[(2-Hydroxydibenzofuran-1-yl)(phenyl)methyl]acetamide
(6a)
White solid; mp 221–224 °C.
Amidoalkyl Dibenzofuranols 6a–n and Dibenzofuran-
Condensed 1,3-Oxazin-3-ones 7a–e; General Procedure
A stirred mixture of dibenzofuran-2-ol (4) (1 mmol), aldehyde 5 (1
mmol), amide or urea (1 mmol) and SnCl2·2H2O (20 mol%) was
heated at 125 °C for the time specified in Table 2. The reaction mix-
ture was cooled to r.t., H2O (20 mL) was added, and the product was
extracted with EtOAc (3 × 15 mL). The combined organic layer was
washed with brine (2 × 5 mL), dried over anhyd Na2SO4 and evap-
orated under vacuum. Recrystallization of the residue from CHCl3–
hexane (1:3) yielded the pure amidoalkyl dibenzofuranol 6a–n as a
crystalline solid. Compounds 7a–e were obtained by heating the re-
action mixture at 160 °C for the time specified in Table 3 followed
by similar work-up.
IR (KBr): 3401, 3180, 1640, 1514, 1435, 1368, 1223 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.35 (s, 1 H), 8.15 (d, J = 7.9
Hz, 1 H), 8.05 (d, J = 8.4 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 1 H), 7.45–
7.10 (m, 9 H), 7.00 (d, J = 8.8 Hz, 1 H), 2.02 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C21H17O3NNa: 354.1106;
found: 354.1116.
N-[(4-Chlorophenyl)(2-hydroxydibenzofuran-1-yl)meth-
yl]acetamide (6b)
White solid; mp 220–222 °C.
IR (KBr): 3400, 3166, 1637, 1509, 1431, 1365, 1219, 1086 cm–1.
Synthesis 2010, No. 6, 959–966 © Thieme Stuttgart · New York

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S. Kantevari et al.
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N-[(4-Bromophenyl)(2-hydroxydibenzofuran-1-yl)meth-
yl]urea (6h)
White solid; mp 78–82 °C.
1H NMR (300 MHz, DMSO-d6): d = 9.40 (s, 1 H), 8.15 (d, J = 7.9
Hz, 1 H), 8.02 (d, J = 8.1 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 1 H), 7.43–
7.15 (m, 8 H), 7.00 (d, J = 8.6 Hz, 1 H), 2.02 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C21H16O3NClNa: 388.0716;
found: 388.0708.
IR (KBr): 3374, 2923, 2853, 1647, 1597, 1528, 1454, 1429, 1369,
1219, 1181, 1076 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.50 (s, 1 H), 8.20 (br s, 1 H),
7.60 (d, J = 8.1 Hz, 1 H), 7.50–7.23 (m, 5 H), 7.20 (d, J = 8.3 Hz, 2
H), 7.00 (s, 3 H), 5.80 (s, 2 H).
13C NMR (75 MHz, DMSO-d6): d = 158.4, 156.1, 151.2, 149.2,
142.7, 130.8, 129.0, 128.0, 127.2, 122.7, 122.4, 122.1, 121.8, 119.2,
116.0, 111.7, 110.8, 49.3.
N-[(4-Chlorophenyl)(2-hydroxydibenzofuran-1-yl)meth-
yl]urea (6c)
Light-yellow solid; mp 68–71 °C.
IR (KBr): 3384, 3063, 2922, 2852, 1701, 1638, 1590, 1461, 1431,
1216, 1154, 1092 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.32 (s, 1 H), 8.15 (d, J = 6.9
Hz, 1 H), 7.75 (s, 1 H), 7.50 (d, J = 8.1 Hz, 1 H), 7.40 (t, J = 7.9 Hz,
1 H), 7.32–7.10 (m, 7 H), 7.00 (d, J = 8.6 Hz, 1 H), 5.55 (s, 2 H).
HRMS (ESI): m/z [M + Na]+ calcd for C20H15O3N2BrNa: 433.0163;
found: 433.0152.
HRMS (ESI): m/z [M + Na]+ calcd for C20H15O3N2ClNa: 389.0668;
found: 389.0685.
N-[(2-Bromophenyl)(2-hydroxydibenzofuran-1-yl)meth-
yl]acetamide (6i)
White solid; mp 208–210 °C.
N-[(4-Chlorophenyl)(2-hydroxydibenzofuran-1-yl)meth-
yl]benzamide (6d)
Yellow solid; mp 210–212 °C.
IR (KBr): 3236, 2925, 1637, 1522, 1435, 1352, 1221, 1083 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.80 (s, 1 H), 8.82 (d, J = 9.6
Hz, 1 H), 8.20 (d, J = 7.5 Hz, 1 H), 7.87 (d, J = 6.6 Hz, 2 H), 7.80
(m, 1 H), 7.55–7.37 (m, 9 H), 7.20 (d, J = 8.4 Hz, 2 H), 7.07 (d,
J = 8.6 Hz, 1 H).
IR (KBr): 3404, 3057, 2925, 1640, 1519, 1430, 1373, 1219, 1082,
1020 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.10 (s, 1 H), 8.25 (d, J = 7.3
Hz, 1 H), 7.87 (s, 1 H), 7.55 (d, J = 7.3 Hz, 1 H), 7.50 (m, 1 H),
7.45–7.23 (m, 4 H), 7.10 (d, J = 7.3 Hz, 3 H), 6.92 (d, J = 8.3 Hz, 1
H), 2.00 (s, 3 H).
13C NMR (75 MHz, CDCl3–DMSO-d6): d = 167.0, 158.8, 154.2,
149.9, 149.2, 138.3, 130.4, 128.4, 126.6, 121.9, 121.3, 120.4, 117.7,
114.3, 109.5, 109.1, 108.5, 49.5, 20.4.
HRMS (ESI): m/z [M + Na]+ calcd for C26H18O3NClNa: 450.0872;
found: 450.0875.
HRMS (ESI): m/z [M + Na]+ calcd for C21H16O3NBrNa: 432.0207;
found: 432.0211.
N-[(2-Hydroxydibenzofuran-1-yl)(3,4,5-trimethoxyphen-
yl)methyl]acetamide (6e)
White solid; mp 183–186 °C.
N-[(2-Hydroxydibenzofuran-1-yl)(4-methoxyphenyl)meth-
yl]acetamide (6j)
IR (KBr): 3373, 3176, 2934, 1632, 1591, 1508, 1454, 1377, 1329,
1240, 1127, 1006 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.42 (s, 1 H), 8.20–8.10 (m, 2
H), 7.55–7.20 (m, 4 H), 7.15 (d, J = 9.0 Hz, 1 H), 7.05 (d, J = 8.6
Hz, 1 H), 6.50 (s, 2 H), 3.62 (s, 9 H), 2.00 (s, 3 H).
White solid; mp 190–192 °C.
IR (KBr): 3407, 3268, 2929, 1644, 1607, 1512, 1433, 1370, 1249,
1220, 1174 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 9.40 (s, 1 H), 8.10 (d, J = 7.9
Hz, 2 H), 7.50–7.17 (m, 7 H), 7.04 (d, J = 7.3 Hz, 1 H), 6.76 (d,
J = 7.3 Hz, 2 H), 3.70 (s, 3 H), 2.02 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C24H23O6NNa: 444.1429;
found: 444.1426.
13C NMR (75 MHz, DMSO-d6): d = 169.0, 157.9, 156.0, 151.2,
149.1, 133.1, 128.3, 127.0, 123.5, 122.5, 121.5, 116.1, 113.4, 111.6,
110.7, 54.9, 49.0, 22.6.
HRMS (ESI): m/z [M + Na]+ calcd for C22H19O4NNa: 384.1211;
found: 384.1217.
N-[(2-Hydroxydibenzofuran-1-yl)(3,4,5-trimethoxyphen-
yl)methyl]benzamide (6f)
White-yellow solid; mp 122–126 °C.
IR (KBr): 3368, 3172, 2934, 2833, 1658, 1578, 1508, 1454, 1408,
1327, 1237, 1123, 1001 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.84 (s, 1 H), 8.90 (d, J = 9.0
Hz, 1 H), 8.24 (d, J = 7.9 Hz, 1 H), 7.92–7.80 (m, 3 H), 7.54–7.30
(m, 7 H), 7.10 (d, J = 8.8 Hz, 1 H), 6.62 (s, 2 H), 3.70 (s, 9 H).
N-[(2-Hydroxydibenzofuran-1-yl)(4-methoxyphenyl)meth-
yl]urea (6k)
White solid; mp 76–79 °C.
IR (KBr): 3373, 2924, 2853, 1648, 1604, 1510, 1455, 1429, 1375,
1247, 1028 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C29H25O6NNa: 506.1620;
found: 506.1612.
1H NMR (300 MHz, DMSO-d6): d = 9.42 (s, 1 H), 8.10 (s, 1 H),
7.56 (d, J = 8.4 Hz, 1 H), 7.43–7.23 (m, 3 H), 7.20 (d, J = 8.4 Hz, 2
H), 7.00 (s, 3 H), 6.75 (d, J = 8.3 Hz, 2 H), 5.70 (s, 2 H), 3.70 (s, 3
H).
13C NMR (75 MHz, DMSO-d6): d = 158.4, 157.7, 156.0, 151.1,
149.0, 134.8, 131.7, 127.0, 123.6, 122.7, 122.0, 116.0, 114.5, 113.3,
112.8, 111.6, 110.4, 54.9, 49.3.
N-[(2-Hydroxydibenzofuran-1-yl)(3,4,5-trimethoxyphen-
yl)methyl]urea (6g)
White solid; mp 161–163 °C.
IR (KBr): 3445, 3374, 2927, 2852, 1647, 1595, 1528, 1455, 1381,
1327, 1240, 1124, 1004 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.30 (d, J = 6.6 Hz, 1 H), 8.20
(br s, 1 H), 7.80 (br s, 1 H), 7.50 (d, J = 8.3 Hz, 1 H), 7.43–7.20 (m,
3 H), 7.10 (d, J = 9.6 Hz, 1 H), 7.00 (d, J = 8.4 Hz, 1 H), 6.60 (s, 2
H), 5.50 (br s, 2 H), 3.60 (s, 9 H).
HRMS (ESI): m/z [M + Na]+ calcd for C21H18O4N2Na: 385.1164;
found: 385.1154.
N-[1-(2-Hydroxydibenzofuran-1-yl)-3-phenylprop-2-en-1-
yl]acetamide (6l)
HRMS (ESI): m/z [M + Na]+ calcd for C23H22O6N2Na: 445.1375;
found: 445.1368.
White solid; mp 155–160 °C.
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Synthesis of Dibenzofuranol Derivatives
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IR (KBr): 3399, 3066, 2924, 1639, 1513, 1451, 1429, 1371, 1271,
1219, 1087 cm–1.
1-(4-Methoxyphenyl)-1,2-dihydro-4,7-dioxa-2-azabenzo[c]fluo-
ren-3-one (7d)
White solid; mp 189–193 °C.
IR (KBr): 3259, 2922, 1729, 1433, 1217, 1163, 1082, 1003 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.70–7.10 (m, 9 H), 6.80 (d,
J = 9.0 Hz, 1 H), 6.70 (s, 1 H), 6.10 (s, 1 H), 3.60 (s, 3 H).
1H NMR (300 MHz, DMSO-d6): d = 9.50 (d, J = 6.4 Hz, 1 H), 8.30
(d, J = 8.6 Hz, 1 H), 7.80 (d, J = 10.0 Hz, 1 H), 7.50–7.05 (m, 10 H),
7.02 (d, J = 8.4 Hz, 1 H), 6.74–6.52 (m, 2 H), 2.00 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C23H19O3NNa: 380.1262;
found: 380.1273.
13C NMR (75 MHz, CDCl3–DMSO-d6): d = 158.9, 156.1, 151.8,
149.4, 145.9, 133.5, 128.3, 127.8, 123.0, 122.8, 122.1, 119.6, 115.9,
115.5, 114.3, 112.1, 111.7, 55.0, 53.3.
HRMS (ESI): m/z [M + Na]+ calcd for C21H15O4N: 368.0898;
found: 368.0906.
N-[Furyl-(2-hydroxydibenzofuran-1-yl)methyl]acetamide (6m)
White solid; mp 155–160 °C.
IR (KBr): 3407, 3181, 2924, 2853, 1645, 1514, 1430, 1369, 1335,
1302, 1272, 1223, 1145 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 9.30 (s, 1 H), 8.15 (d, J = 7.9
Hz, 1 H), 7.95 (d, J = 8.7 Hz, 1 H), 7.47 (m, 1 H), 7.40–7.20 (m, 5
H), 7.00 (d, J = 8.9 Hz, 1 H), 6.22 (s, 1 H), 6.10 (s, 1 H), 2.00 (s, 3
H).
1-(3,4,5-Trimethoxyphenyl)-1,2-dihydro-4,7-dioxa-2-azaben-
zo[c]fluoren-3-one (7e)
White solid; mp 167–172 °C.
IR (KBr): 3369, 2930, 1735, 1591, 1505, 1458, 1426, 1231, 1124
cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C19H15O4NNa: 344.0898;
found: 344.0890.
1H NMR (300 MHz, DMSO-d6): d = 8.58 (d, J = 2.4 Hz, 1 H), 7.70–
7.50 (m, 4 H), 7.40 (t, J = 8.1 Hz, 1 H), 7.25–7.15 (m, 1 H), 6.55 (s,
2 H), 6.08 (d, J = 2.8 Hz, 1 H), 3.70 (s, 9 H).
HRMS (ESI): m/z [M + Na]+ calcd for C23H19O6NNa: 428.1110;
found: 428.1115.
N-[(2-Hydroxydibenzofuran-1-yl)(1H-indol-3-yl)methyl]acet-
amide (6n)
Brick-red solid; mp 125–130 °C.
IR (KBr): 3405, 2924, 1717, 1645, 1514, 1428, 1379, 1220, 1166,
744 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 10.40 (br s, 1 H), 9.30 (br s, 1
H), 8.10 (s, 1 H), 7.76 (m, 2 H), 7.60 (d, J = 7.7 Hz, 1 H), 7.50 (m,
1 H), 7.40–7.26 (m, 3 H), 7.20 (t, J = 7.9 Hz, 1 H), 7.05 (d, J = 8.4
Hz, 1 H), 7.00–6.95 (m, 2 H), 6.80 (s, 1 H), 2.00 (s, 3 H).
Acknowledgment
The authors are grateful to Dr. J. S. Yadav, Director and Dr. V. V.
N. Reddy, Head, Organic Chemistry Division-II, IICT, Hyderabad
for their continuous support and encouragement. T.Y. (JRF) and
S.V.N.V. (SRF) are thankful to CSIR for financial assistance.
HRMS (ESI): m/z [M + Na]+ calcd for C23H18O3N2Na: 393.1215;
found: 393.1213.
References
1-(4-Chlorophenyl)-1,2-dihydro-4,7-dioxa-2-azabenzo[c]fluo-
ren-3-one (7a)
(1) (a) Multicomponent reactions; Zhu, J.; Bienaymé, H., Eds.;
Wiley-VCH: Weinheim, 2005. (b) von Wangelin, A. J.;
Neumann, H.; Gordes, D.; Klaus, S.; Strubing, D.; Beller, M.
Chem. Eur. J. 2003, 9, 4286. (c) Dömling, A. Chem. Rev.
2006, 106, 17. (d) Orru, R. V. A.; de Greef, M. Synthesis
2003, 1471. (e) Hulme, C.; Gore, V. Curr. Med. Chem.
2003, 10, 51. (f) Ramón, D. J.; Yus, M. Angew. Chem. Int.
Ed. 2005, 44, 1602.
White solid; mp 127–132 °C.
IR (KBr): 3252, 2923, 1728, 1431, 1386, 1216, 1163, 1090 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 8.75 (s, 1 H), 7.60–7.54 (m, 3
H), 7.43 (t, J = 7.4 Hz, 1 H), 7.36–7.25 (m, 5 H), 7.20 (t, J = 7.4 Hz,
1 H), 6.20 (s, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C20H12O3NClNa: 372.0403;
found: 372.0399.
(2) (a) Ganem, B. Acc. Chem. Res. 2009, 42, 463. (b) Isambert,
N.; Lavilla, R. Chem. Eur. J. 2008, 14, 8444.
1-(4-Bromophenyl)-1,2-dihydro-4,7-dioxa-2-azabenzo[c]fluo-
ren-3-one (7b)
White solid; mp 189–193 °C.
IR (KBr): 3259, 2925, 1729, 1433, 1217, 1082, 1003 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 8.70 (s, 1 H), 7.60–7.50 (m, 3
H), 7.48–7.40 (m, 3 H), 7.30-7.15 (m, 4 H), 6.14 (s, 1 H).
13C NMR (75 MHz, CDCl3–DMSO-d6): d = 156.0, 151.7, 149.4,
145.4, 139.3, 131.3, 131.2, 128.2, 126.9, 122.2, 121.8, 121.5, 121.3,
115.2, 113.4, 111.5, 111.1, 53.5.
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(b) Khosropour, A. R.; Khodaei, M. M.; Moghanian, H.
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Sheikhan, N.; Ruoho, A. E. Tetrahedron Lett. 2009, 50,
5649. (c) Shaterian, H. R.; Yarahmadi, H. Tetrahedron Lett.
2008, 49, 1297. (d) Shaterian, H. R.; Yarahmadi, H.;
Ghashang, M. Tetrahedron 2008, 64, 1263. (e) Shaterian,
H. R.; Hosseinian, A.; Ghashang, M. Tetrahedron Lett.
2008, 49, 5804. (f) Dorehgiraee, A.; Khabazzadeh, H.;
Saidi, K. ARKIVOC 2009, (vii), 303. (g) Shaterian, H. R.;
Hosseinian, A.; Ghashang, M. Bioorg. Med. Chem. Lett.
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(b) Dabiri, M.; Delbari, A. S.; Bazgir, A. Heterocycles 2007,
71, 543.
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MS (EI): m/z = 395 [M + 2]+, 393 [M]+.
1-p-Tolyl-1,2-dihydro-4,7-dioxa-2-azabenzo[c]fluoren-3-one
(7c)
White solid; mp 168–172 °C.
IR (KBr): 3244, 3126, 2923, 1726, 1432, 1398, 1219, 1165 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.60–7.27 (m, 6 H), 7.20–7.00 (m,
4 H), 6.75 (s, 1 H), 6.05 (s, 1 H), 2.25 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C21H15O3NNa: 352.0950;
found: 352.0956.
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S. Kantevari et al.
PAPER
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Synthesis 2010, No. 6, 959–966 © Thieme Stuttgart · New York