Reductive cyclization of nitro and azide compounds with aldehydes and ketones promoted by metallic samarium and catalytic amount of iodine

Article abstract of DOI:10.1071/CH02117

Reductive cyclization of nitro and azide compounds was discussed. The cyclization was done with aldehydes and ketones which is promoted by metallic samarium and catalytic amount of iodine. Results showed that three equivalents of samarium were required when the substrate was a nitro compound and one equivalent of samarium was needed for the azide compounds.

Full text of DOI:10.1071/CH02117

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Aust. J. Chem. 2002, 55, 695–697
Reductive Cyclization of Nitro and Azide Compounds with
Aldehydes and Ketones Promoted by Metallic Samarium
and Catalytic Amount of Iodine
Weike SuA,B and Bibo YangA
A
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, P.R. China.
Author to whom correspondence should be addressed (e-mail: suweike@zjut.edu.cn).
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Manuscript received: 6 June 2002.
Final version: 9 October 2002.
Since pioneering studies by Kagan and his group
demonstrated the particular effectiveness of samarium
O
X
CONH2
Y
X
NH
1
2
Sm / I2 (cat.)
+
R COR
R1
R2
diiodide (SmI2) as
one-electron transfer reducing agent,
SmI in synthetic organic chemistry has been extensively
a
mild, neutral, ether-soluble,
[
1,2]
the utilization of
N
H
(1)
X = H , Cl Y = NO2 , N3
(2)
(3)
2
[3–10]
documented.
However, problems can arise when SmI is
2
Scheme 1
used as a reductant. SmI is available in sealed bottles, but
2
can be inactivated even after a brief exposure to air and/or
corresponding aldehydes or ketones (2) were introduced and
the desired products, 2,3-dihydro-2-aryl-4(1H)-quinazol-
inones (3), were formed. The results are presented in Table 1.
We found that, when the substrate (1) was a nitro
compound, three equivalents of samarium was required for
completion of the reaction. Only one equivalent of samarium
was needed for the azide compounds. Table 1 shows that
aldehydes and aliphatic ketones can react with substrates (1)
to afford the desired products (3) in satisfactory yields.
However, for aromatic ketones, only 2-aminobenzamides
were obtained and products (3) were not detected even when
moisture, and SmI invariably cannot meet the demand of
2
atom economy. On the other hand, metallic samarium is
3
+
stable in air, and its strong reducing power (Sm /Sm =
2
+
–
–
2.41 V) is similar to that of magnesium (Mg /Mg =
2.37 V). It has been noted recently that metallic samarium
[
11–15]
can be used directly in organic synthesis.
we wish to use the more convenient and cheaper samarium,
instead of SmI , directly as a reductant.
As a result,
2
2,3-Dihydro-2-aryl-4(1H)-quinazolinone derivatives are
important compounds for pharmaceutical chemistry. Some
[
16,17]
are herbicides and plant-growth regulators.
also used as diuretics and antitumour agents.[
They are
A general
18,19]
Table 1. Reductive cyclization of nitro and azide compounds
with aldehydes and ketones promoted by metallic samarium and
a catalytic amount of iodine
procedure for the preparation of 2,3-dihydro-2-aryl-4(1H)-
quinazolinones involves condensing the appropriate
2-aminobenzamide with an aldehyde or ketone using
Entry
X
Y
R1
Bun
C H
R2 Yield (%)A
p-toluenesulfonic acid as a catalyst under vigorous reaction
[20,21]
conditions.
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
NO2
NO2
NO2
NO2
H
H
H
H
H
69 (3a)
83 (3b)
80 (3c)
85 (3d)
81 (3e)
80 (3f)
It is well known that nitro and azide compounds can easily
be reduced to their corresponding amines by metallic
samarium and catalytic amounts of iodine.[22,23] However,
little attention has been paid to the intermediate derived from
6
5
4-ClC H
6
4
3-BrC6H4
NO2
4-CH OC H
4
3
6
[24]
N3
CH CH CH CH
2
H
3
2
2
a nitro or azide group by the reduction treatment. In our
previous work, we demonstrated the reductive coupling of
azide compounds with nitriles induced by samarium
B
NO2
NO2
N3
N3
N3
N3
N3
N3
4-ClC H
CH3
C H
0
6
4
B
C H
0
6
5
6
5
C H
H
H
H
89 (3g)
86 (3h)
88 (3i)
80 (3j)
77 (3k)
6
5
[25]
diiodide.
Herein, we wish to report the reductive
1
0
2-fural
3-thieyl
CH3CH2CH2
cyclization of nitro and azide compounds with aldehydes and
ketones promoted by metallic samarium and catalytic
amounts of iodine (Scheme 1).
After treating o-nitrobenzamide or o-azidobenzamide (1)
with metallic samarium and catalytic amounts of iodine in
anhydrous methanol under a nitrogen atmosphere, the
11
12
CH3
1
1
3
4
–(CH ) –
2 5
B
C H
CH3
0
6
5
A
B
Isolated yields based on nitro and azide compounds.
Reaction conditions: 20 h in refluxing methanol.
©
CSIRO 2002
10.1071/CH02117
0004-9425/02/110695

6
96
W. Su and B. Yang
reflux conditions were maintained for a long time. If
o-aminobenzamides derived from compounds (1) were
treated with aldehydes and ketones (2) under the same
conditions, product (3) could not be detected. It was also
found that this reaction could proceed with previously
which was stirred at room temperature for 2–3 h. The aldehyde or ketone
(2) (1.2 mmol) in 5 mL methanol was then introduced. After being
stirred for 3 h in refluxing conditions, the solvent was removed under
reduced pressure. The residue was treated with dilute HCl (0.01 M,
20 mL) and extracted with ethyl acetate (3×20 mL). The organic layer
was washed with a saturated aqueous solution of Na S O (15 mL) and
2
2
3
formed SmI , but six equivalents and two equivalents of
brine (15 mL), respectively, and dried over anhydrous MgSO4. After the
ethyl acetate was removed under reduced pressure, the desired product
was obtained by recrystallization from anhydrous ethanol.
2
SmI were consumed for the reaction of nitro and azide
2
[
26,27]
compounds, respectively, under similar conditions.
The
1
remarkable advantage of the reaction we have described here
is atom economy. Although the detailed mechanism of the
above reaction is not certain, the formation of products (3)
may be described by the possible mechanism presented in
Scheme 2.
(3a). M.p. 144–146°C. H NMR ((D )DMSO) 0.88, t, J 7.0 Hz,
6
3
H, CH ; 1.30–1.62, m, 6H, 3×CH ; 6.57, br s, 1H, NH; 6.72, d, J 8.0
3
2
1
3
Hz, 1H, CH; 7.22–7.57, m, 4H, ArH; 7.88, br s, 1H, NH. C NMR
(D )DMSO) 163.97, 148.58, 133.09, 127.41, 116.91, 115.07, 114.43,
(
6
64.48, 34.81, 25.49, 22.15, 14.02. Found C, 70.5; H, 8.0; N, 13.7%.
C H N O requires C, 70.6; H, 7.9; N, 13.7%.
1
2
16
2
(
3b).
M.p. 221–222°C (Lit.[28] 220–222°C). 1H NMR
Sm
+
I2 (cat.)
(
(D )DMSO) 5.78, br s, 1H, NH; 6.77, d, J 8.0 Hz, 1H, CH; 7.15–7.64,
6
1
3
m, 9H, ArH; 8.32, br s, 1H, NH. C NMR ((D )DMSO) 163.65,
6
1
1
47.93, 147.71, 136.36, 128.51, 128.38, 128.12, 127.41, 126.93,
20.76, 117.17, 115.02, 114.46, 66.62.
low valent Sm
substrates 1
products 3
(
3c). M.p. 205–206°C (Lit.[28] 204–205°C). 1H NMR
(D )DMSO) 5.77, br s, 1H, NH; 6.68, d, J 7.5 Hz, 1H, CH; 7.25–7.60,
(
6
1
3
m, 8H, ArH; 8.34, br s, 1H, NH. C NMR ((D )DMSO) 163.54,
47.73, 140.76, 133.46, 133.30, 128.82, 128.38, 127.43, 126.17,
21.09, 117.34, 115.01, 114.53, 65.82.
6
1
1
3+
1
Sm
(3d). M.p. 231–232°C. H NMR ((D )DMSO) 5.94, br s, 1H,
Sm
6
NH; 6.78, d, J 8.0 Hz, 1H, CH; 7.27–7.70, m, 8H, ArH; 8.53, br s, 1H,
1
3
X
X
CONH2
NH. C NMR ((D )DMSO) 163.40, 147.77, 147.37, 144.36, 133.65,
1
6
33.45, 130.13, 127.48, 123.35, 121.63, 117.60, 115.02, 114.66, 65.24.
Found C, 55.5; H, 4.0; N, 9.1%. C H BrN O requires C, 55.5; H, 3.7;
N, 9.2%.
N3
X
CONH2
14 11
2
1
X
CONH2
CONH2
low valent Sm
2 -
N
1
(
3e). M.p. 180–182°C. H NMR ((D )DMSO) 2.29, s, 3H, CH ;
5.70, br s, 1H, NH; 6.73, d, J 8.0 Hz, 1H, CH; 7.19–7.59, m, 8H, ArH;
.22, br s, 1H, NH. C NMR ((D )DMSO) 163.76, 159.50, 148.09,
6
3
NO2
NO
O
1
1
3
8
O
6
X
X
133.58, 133.29, 128.27, 128.03, 127.41, 121.57, 117.12, 115.07,
14.49, 113.70, 66.34, 55.24. Found C, 70.1; H, 5.4; N, 10.8%.
C H N O requires C, 70.9; H, 5.6; N, 11.0%.
X
R COR
CONH2
+
1
2
H O
NH
NH
3
1
1
1
1
R
R
R
-
-
-
2
2
2
R
N
H
R
15 14
2
2
N
C
O
R
N
-
3
1
(
3f). M.p. 144–145°C. H NMR ((D )DMSO) 0.88, t, J 7.0 Hz,
6
3
H, CH ; 1.30–1.62, m, 6H, 3×CH ; 6.57, br s, 1H, NH; 6.72, d, J 8.0
3
2
Scheme 2
1
3
Hz, 1H, CH; 7.22–7.57, m, 4H, ArH; 7.88, br s, 1H, NH. C NMR
(D )DMSO) 163.97, 148.58, 133.09, 127.41, 116.91, 115.07, 114.43,
(
6
6
4.48, 34.81, 25.49, 22.15, 14.02. Found C, 70.1; H, 7.7; N, 13.6%.
In summary, the intermolecular reductive cyclization
reaction of nitro and azide compounds with aldehydes and
C H N O requires C, 70.6; H, 7.9; N, 13.7%.
1
2
16
2
1
(
3g). M.p. 248–249°C. H NMR ((D )DMSO) 5.79, br s, 1H,
ketones was studied, and
a
facile synthesis of
6
NH; 6.77, d, J 8.8 Hz, 1H, CH; 7.21–7.55, m, 8H, ArH; 8.53, br s, 1H,
NH. C NMR ((D )DMSO) 162.34, 146.46, 141.31, 132.99, 128.56,
2,3-dihydro-2-aryl-4(1H)-quinazolinones was provided. Our
1
3
6
method for the preparation of these compounds circumvents
many problems that occurred in previous preparation
processes. Further studies to develop other new reactions
using metallic samarium are now in progress.
128.40, 128.27, 127.77, 126.63, 126.27, 120.54, 116.38, 115.84, 66.06.
Found C, 65.1; H, 4.1; N, 10.0%. C H ClN O requires C, 65.0; H, 4.3;
N, 10.8%.
14
11
2
1
(
3h). M.p. 202°C; H NMR ((D )DMSO) 5.79, br s, 1H, NH;
6
6
.27–6.42, m, 2H, ArH; 6.74, d, J 8.6 Hz, 1H, CH; 7.21–7.63, m, 4H,
Experimental
13
ArH; 8.58, br s, 1H, NH. C NMR ((D )DMSO) 162.04, 154.05,
6
1
1
45.81, 142.80, 132.92, 126.23, 120.80, 116.42, 115.96, 110.23,
All reactions were performed under a dry nitrogen atmosphere. Melting
1
07.18, 59.95. Found C, 57.5; H, 3.8; N, 11.4%. C H ClN O requires
points were uncorrected. Nuclear magnetic resonance spectra ( H NMR
12
9
2
2
13
C, 58.0; H, 3.6; N, 11.3%.
and C NMR) were determined using a Bruker AC-400 instrument
with dimethyl sulfoxide ((D )DMSO) as the solvent. Chemical shifts
are expressed in ppm downfield from internal tetramethylsilane.
Microanalysis was carried out on a Carlo-Erba 1106 instrument.
1
6
(
3i). M.p. 216–218°C; H NMR ((D )DMSO) 5.82, br s, 1H, NH;
6
6
.72, d, J 8.6 Hz, 1H, CH; 7.13–7.54, m, 6H, ArH; 8.51, br s, 1H, NH.
C NMR ((D )DMSO) 162.24, 146.36, 143.21, 132.93, 126.82,
13
6
1
26.30, 126.16, 123.17, 120.72, 116.43, 116.08, 62.35. Found C, 54.3;
General Procedures
H, 3.7; N, 11.1%. C H ClN OS requires C, 54.4; H, 3.4; N, 10.6%.
1
2
9
2
0.15 g (1 mmol) (0.45 g when the substrates (1) were nitro compounds)
1
of metallic samarium and 0.05 g (0.2 mmol) of iodine were mixed in a
three-neck round-bottomed flask under dry nitrogen. 1 mmol of azide
(3j). M.p. 231–233°C; H NMR ((D )DMSO) 1.08 t, J 9.0 Hz,
6
3H, CH ; 1.52, s, 3H, CH ; 2.26–2.50, m, 4H, CH CH ; 7.03, br s, 1H,
NH; 7.46–7.76, m, 3H, ArH; 8.05, br s, 1H, NH. C NMR
3
3
2
2
1
3
(or nitro) compounds in 10 mL methanol was added to the mixture,

Samarium Promoted Reductive Cyclization Reactions
697
(
(D )DMSO) 161.32, 140.58, 135.08, 132.10, 129.21, 125.33, 122.35,
[10] G. A. Molander, C. R. Harris, Chem. Rev. 1996, 96, 307.
6
6
5.36, 35.12, 22.37, 15.95, 15.60. Found C, 56.3; H, 5.8; N, 11.2%.
[11] Y. Taniguchi, N. Fujii, K. Takaki, Y. Fujiwara, J. Organomet.
Chem. 1995, 491, 173.
C H ClN O requires C, 56.6; H, 5.9; N, 11.0%.
1
2
15
2
[
[
12] M. Lautens, P. H. Delanghe, J. Org. Chem. 1995, 60, 2474.
13] R. Yanada, N. Negoro, K. Yanada, T. Fujita, Tetrahedron Lett.
1
(
3k). M.p. 241°C; H NMR ((D )DMSO) 1.55–1.64, m, 10H,
6
5
×CH ; 6.85, br s, 1H, NH; 7.19–7.52, m, 3H, ArH; 8.10, br s, 1H, NH.
C NMR ((D )DMSO) 161.98, 145.42, 132.81, 126.11, 120.06,
16.51, 115.48, 67.96, 37.03, 24.46, 20.76. Found C, 58.6; H, 5.7; N,
0.0%. C H ClN O requires C, 58.5; H, 5.6; N, 10.5%.
2
1
996, 37, 9313.
14] R. Yanada, N. Negoro, K. Yanada, T. Fujita, Tetrahedron Lett.
997, 38, 3271.
1
3
6
[
1
1
1
13
15
2
[
[
15] L. Wang, Y. M. Zhang, Tetrahedron 1998, 54, 11129.
16] P. R. Bhalla, B. L. Walworth, American Cyanamid Co. Eur. Pat.
Appl. EP 58,822; Chem. Abstr. 1983, 98, 1669.
Acknowledgments
We are grateful to the Centre of Engineering Research of
Zhejiang University of Technology for financial help.
[17] P. R. Bhalla, B. L. Walworth, American Cyanamid Co. U. S.
Patent 4,431,440; Chem. Abstr. 1984, 100, 174857.
[18] M. G. Biressi, G. Cantarelli, M. Carissimi, A. Cattaneo, F.
Ravenna, Farmaco, Ed. Sci. 1969, 24, 199.
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